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More weight loss linked with more benefit in STEP-HFpEF
AMSTERDAM – , including symptoms and physical limitations, exercise capacity, and inflammation, new analyses from the trial show.
At the annual congress of the European Society of Cardiology where he presented these new findings, Mikhail N. Kosiborod, MD, also posited that weight loss produced by weekly subcutaneous injections of 2.4 mg semaglutide (Wegovy) for 52 weeks in the study does not fully explain the multiple mechanisms that may be involved in producing this intervention’s effects in the STEP-HFpEF trial.
His report earlier at the congress and in a simultaneously published report of the trial’s primary outcomes established a role for medically induced weight loss in managing patients with obesity-phenotype HFpEF in a total of 529 randomized individuals with HFpEF and obesity but without diabetes.
The new analyses showed that for one of the two primary endpoints – the change from baseline in patients’ assessment on the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ), the placebo-adjusted average change was a 16.1-point improvement in the 51 people with a 5%-10% weight loss during the 1-year study, and a 21.6-point improvement in the 58 who had at least a 20% weight loss, a between-group average 5.5 point difference that represents a clinically meaningful incremental improvement in this validated metric of symptoms and functional limitations.
Similar weight-related differences in benefit also occurred for the secondary outcomes of changes from baseline in 6-minute walk distance and in levels of C-reactive protein (CRP), a measure of systemic inflammation.
In an adjusted regression model, every 10% drop from baseline body weight was significantly linked with a 6.4-point improvement in KCCQ score, a 14.4 meter improvement in 6-minute walk distance, and a 28% relative reduction from baseline in CRP, reported Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo.
These new, prespecified analyses also showed that people with obesity and HFpEF responded roughly the same to semaglutide treatment compared with placebo-treated controls regardless of their starting body mass index, including people with class 1 (30-34 kg/m2), class 2 (35-39 kg/m2), and class 3 (≥ 40 kg/m2) obesity.
Simultaneously with Dr. Kosiborod’s report at the congress, these findings appeared in a report posted online in Nature Medicine.
Not every benefit was fully mediated by weight loss
These analyses “do not tell us how much of the benefit was mediated by weight loss, but the data do say that the more weight a person lost, the more benefit they got,” Dr. Kosiborod explained in an interview. “That is not the same as saying that everything is mediated by weight. It doesn’t say that nothing beyond weight loss matters.”
He and his associates are planning a mediation analysis of data from STEP-HFpEF that will more directly address this issue.
“It’s likely that people who lost more weight with semaglutide also had greater benefits from other effects of semaglutide at the same time. Weight loss is a good surrogate marker” for the range of effects that a person receives from treatment with semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, Dr. Kosiborod said.
“GLP-1 receptor agonists may have direct effects on atherosclerosis, as well as other effects that are uncoupled from weight loss,” such as proven anti-inflammatory effects, he added.
Another exploratory effect from semaglutide treatment in the study and reported by Dr. Kosiborod was a significant reduction in serum levels of N-terminal pro brain natriuretic peptide, an association never previously seen with weight loss in people with heart failure.
“The outcomes we’ve already seen in STEP-HFpEF were largely symptomatic, which are extraordinarily important, but there may be a completely different relationship between weight and clinical events,” said John E. Deanfield, PhD, a professor of cardiology at University College Hospital, London, who was not involved in the study.
Dr. Deanfield noted that important prognostic markers such as cholesterol levels and blood pressure reductions are usually not temporally related to weight loss. “The idea that [the benefits seen in STEP-HFpEF] are purely from weight loss is something we need to be careful about,” he said.
“My gut feeling is that at least 75% of the effect [in STEP-HFpEF} was due to weight loss,” said Naveed Sattar, PhD, professor of metabolic medicine at the University of Glasgow, who was not associated with the research.
STEP-HFpEF was funded by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Kosiborod has been a consultant and adviser to, and has received honoraria from, Novo Nordisk. He has been a consultant to numerous other companies, received research grants from AstraZeneca, Boehringer Ingelheim, and Pfizer, honoraria from AstraZeneca, and is a stockholder in Artera Health and Saghmos Therapeutics. Dr. Deanfield has been a consultant to Novo Nordisk as well as to Aegerion, Amgen, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Sanofi, and Takeda, and has received research funding from Aegerion, Colgate, MSD, Pfizer, and Roche. Dr. Sattar has been a consultant to Novo Nordisk as well as to Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Pfizer, and Roche Diagnostics.
A version of this article first appeared on Medscape.com.
AMSTERDAM – , including symptoms and physical limitations, exercise capacity, and inflammation, new analyses from the trial show.
At the annual congress of the European Society of Cardiology where he presented these new findings, Mikhail N. Kosiborod, MD, also posited that weight loss produced by weekly subcutaneous injections of 2.4 mg semaglutide (Wegovy) for 52 weeks in the study does not fully explain the multiple mechanisms that may be involved in producing this intervention’s effects in the STEP-HFpEF trial.
His report earlier at the congress and in a simultaneously published report of the trial’s primary outcomes established a role for medically induced weight loss in managing patients with obesity-phenotype HFpEF in a total of 529 randomized individuals with HFpEF and obesity but without diabetes.
The new analyses showed that for one of the two primary endpoints – the change from baseline in patients’ assessment on the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ), the placebo-adjusted average change was a 16.1-point improvement in the 51 people with a 5%-10% weight loss during the 1-year study, and a 21.6-point improvement in the 58 who had at least a 20% weight loss, a between-group average 5.5 point difference that represents a clinically meaningful incremental improvement in this validated metric of symptoms and functional limitations.
Similar weight-related differences in benefit also occurred for the secondary outcomes of changes from baseline in 6-minute walk distance and in levels of C-reactive protein (CRP), a measure of systemic inflammation.
In an adjusted regression model, every 10% drop from baseline body weight was significantly linked with a 6.4-point improvement in KCCQ score, a 14.4 meter improvement in 6-minute walk distance, and a 28% relative reduction from baseline in CRP, reported Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo.
These new, prespecified analyses also showed that people with obesity and HFpEF responded roughly the same to semaglutide treatment compared with placebo-treated controls regardless of their starting body mass index, including people with class 1 (30-34 kg/m2), class 2 (35-39 kg/m2), and class 3 (≥ 40 kg/m2) obesity.
Simultaneously with Dr. Kosiborod’s report at the congress, these findings appeared in a report posted online in Nature Medicine.
Not every benefit was fully mediated by weight loss
These analyses “do not tell us how much of the benefit was mediated by weight loss, but the data do say that the more weight a person lost, the more benefit they got,” Dr. Kosiborod explained in an interview. “That is not the same as saying that everything is mediated by weight. It doesn’t say that nothing beyond weight loss matters.”
He and his associates are planning a mediation analysis of data from STEP-HFpEF that will more directly address this issue.
“It’s likely that people who lost more weight with semaglutide also had greater benefits from other effects of semaglutide at the same time. Weight loss is a good surrogate marker” for the range of effects that a person receives from treatment with semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, Dr. Kosiborod said.
“GLP-1 receptor agonists may have direct effects on atherosclerosis, as well as other effects that are uncoupled from weight loss,” such as proven anti-inflammatory effects, he added.
Another exploratory effect from semaglutide treatment in the study and reported by Dr. Kosiborod was a significant reduction in serum levels of N-terminal pro brain natriuretic peptide, an association never previously seen with weight loss in people with heart failure.
“The outcomes we’ve already seen in STEP-HFpEF were largely symptomatic, which are extraordinarily important, but there may be a completely different relationship between weight and clinical events,” said John E. Deanfield, PhD, a professor of cardiology at University College Hospital, London, who was not involved in the study.
Dr. Deanfield noted that important prognostic markers such as cholesterol levels and blood pressure reductions are usually not temporally related to weight loss. “The idea that [the benefits seen in STEP-HFpEF] are purely from weight loss is something we need to be careful about,” he said.
“My gut feeling is that at least 75% of the effect [in STEP-HFpEF} was due to weight loss,” said Naveed Sattar, PhD, professor of metabolic medicine at the University of Glasgow, who was not associated with the research.
STEP-HFpEF was funded by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Kosiborod has been a consultant and adviser to, and has received honoraria from, Novo Nordisk. He has been a consultant to numerous other companies, received research grants from AstraZeneca, Boehringer Ingelheim, and Pfizer, honoraria from AstraZeneca, and is a stockholder in Artera Health and Saghmos Therapeutics. Dr. Deanfield has been a consultant to Novo Nordisk as well as to Aegerion, Amgen, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Sanofi, and Takeda, and has received research funding from Aegerion, Colgate, MSD, Pfizer, and Roche. Dr. Sattar has been a consultant to Novo Nordisk as well as to Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Pfizer, and Roche Diagnostics.
A version of this article first appeared on Medscape.com.
AMSTERDAM – , including symptoms and physical limitations, exercise capacity, and inflammation, new analyses from the trial show.
At the annual congress of the European Society of Cardiology where he presented these new findings, Mikhail N. Kosiborod, MD, also posited that weight loss produced by weekly subcutaneous injections of 2.4 mg semaglutide (Wegovy) for 52 weeks in the study does not fully explain the multiple mechanisms that may be involved in producing this intervention’s effects in the STEP-HFpEF trial.
His report earlier at the congress and in a simultaneously published report of the trial’s primary outcomes established a role for medically induced weight loss in managing patients with obesity-phenotype HFpEF in a total of 529 randomized individuals with HFpEF and obesity but without diabetes.
The new analyses showed that for one of the two primary endpoints – the change from baseline in patients’ assessment on the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ), the placebo-adjusted average change was a 16.1-point improvement in the 51 people with a 5%-10% weight loss during the 1-year study, and a 21.6-point improvement in the 58 who had at least a 20% weight loss, a between-group average 5.5 point difference that represents a clinically meaningful incremental improvement in this validated metric of symptoms and functional limitations.
Similar weight-related differences in benefit also occurred for the secondary outcomes of changes from baseline in 6-minute walk distance and in levels of C-reactive protein (CRP), a measure of systemic inflammation.
In an adjusted regression model, every 10% drop from baseline body weight was significantly linked with a 6.4-point improvement in KCCQ score, a 14.4 meter improvement in 6-minute walk distance, and a 28% relative reduction from baseline in CRP, reported Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo.
These new, prespecified analyses also showed that people with obesity and HFpEF responded roughly the same to semaglutide treatment compared with placebo-treated controls regardless of their starting body mass index, including people with class 1 (30-34 kg/m2), class 2 (35-39 kg/m2), and class 3 (≥ 40 kg/m2) obesity.
Simultaneously with Dr. Kosiborod’s report at the congress, these findings appeared in a report posted online in Nature Medicine.
Not every benefit was fully mediated by weight loss
These analyses “do not tell us how much of the benefit was mediated by weight loss, but the data do say that the more weight a person lost, the more benefit they got,” Dr. Kosiborod explained in an interview. “That is not the same as saying that everything is mediated by weight. It doesn’t say that nothing beyond weight loss matters.”
He and his associates are planning a mediation analysis of data from STEP-HFpEF that will more directly address this issue.
“It’s likely that people who lost more weight with semaglutide also had greater benefits from other effects of semaglutide at the same time. Weight loss is a good surrogate marker” for the range of effects that a person receives from treatment with semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, Dr. Kosiborod said.
“GLP-1 receptor agonists may have direct effects on atherosclerosis, as well as other effects that are uncoupled from weight loss,” such as proven anti-inflammatory effects, he added.
Another exploratory effect from semaglutide treatment in the study and reported by Dr. Kosiborod was a significant reduction in serum levels of N-terminal pro brain natriuretic peptide, an association never previously seen with weight loss in people with heart failure.
“The outcomes we’ve already seen in STEP-HFpEF were largely symptomatic, which are extraordinarily important, but there may be a completely different relationship between weight and clinical events,” said John E. Deanfield, PhD, a professor of cardiology at University College Hospital, London, who was not involved in the study.
Dr. Deanfield noted that important prognostic markers such as cholesterol levels and blood pressure reductions are usually not temporally related to weight loss. “The idea that [the benefits seen in STEP-HFpEF] are purely from weight loss is something we need to be careful about,” he said.
“My gut feeling is that at least 75% of the effect [in STEP-HFpEF} was due to weight loss,” said Naveed Sattar, PhD, professor of metabolic medicine at the University of Glasgow, who was not associated with the research.
STEP-HFpEF was funded by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Kosiborod has been a consultant and adviser to, and has received honoraria from, Novo Nordisk. He has been a consultant to numerous other companies, received research grants from AstraZeneca, Boehringer Ingelheim, and Pfizer, honoraria from AstraZeneca, and is a stockholder in Artera Health and Saghmos Therapeutics. Dr. Deanfield has been a consultant to Novo Nordisk as well as to Aegerion, Amgen, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Sanofi, and Takeda, and has received research funding from Aegerion, Colgate, MSD, Pfizer, and Roche. Dr. Sattar has been a consultant to Novo Nordisk as well as to Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Pfizer, and Roche Diagnostics.
A version of this article first appeared on Medscape.com.
AT THE ESC CONGRESS 2023
Anticoagulation no benefit in presumed AFib detected by cardiac devices
AMSTERDAM – Among patients with atrial high-rate episodes detected by implantable devices, anticoagulation with edoxaban did not significantly reduce the incidence of a composite outcome of cardiovascular death, stroke, or systemic embolism in comparison with placebo but was associated with a higher bleeding risk in the NOAH-AFNET 6 trial.
“ They do not need to be anticoagulated. That is a relief,” the lead investigator of the trial, Paulus Kirchhof, MD, University Heart and Vascular Center Hamburg (Germany), said in an interview.
Dr. Kirchhof pointed out that this result was unexpected. “Many of us thought that because atrial high-rate episodes look like AF[ib] when they occur, then they are an indication for anticoagulation. But based on these results from the first-ever randomized trial on this population, there is no need for anticoagulation in these patients.”
Dr. Kirchhof presented the NOAH-AFNET 6 trial at the annual congress of the European Society of Cardiology. The study was also simultaneously published in the New England Journal of Medicine.
The trial recruited patients with implanted devices that enable continuous monitoring of atrial rhythm, such as pacemakers and defibrillators. “Because we can record the rhythm day and night with these devices, they pick up small abnormalities. About 20% of these patients experience these occasional atrial high-rate episodes – short episodes that look like AF[ib], but they are rare and brief,” Dr. Kirchhof noted.
He explained that whether the occurrence of these atrial high-rate episodes in patients without AFib, as documented on a conventional electrocardiogram, justifies the initiation of anticoagulants has been unclear. “But this trial tells us that these episodes are different to AF[ib] that is diagnosed on ECG,” he added.
Another finding in the trial was that among these patients, there was an unexpectedly low rate of stroke, despite the patients’ having a CHADSVASC score of 4.
“Based on the result of this trial, these occasional atrial high-rate episodes do not appear to be associated with stroke. It appears quite benign,” Dr. Kirchhof said.
Implications for wearable technology?
He said the results may also have implications for wearable devices that pick up abnormal heart rhythm, such as smartwatches.
“We don’t know exactly what these wearable technologies are picking up, but most likely it is these atrial high-rate episodes. But we need more research on the value of these wearable technologies; we need randomized trials in this particular patient population before we consider anticoagulation in these patients,” Dr. Kirchhof stated.
The NOAH-AFNET 6 study was an event-driven, double-blind, double-dummy, randomized trial involving 2,536 patients aged 65 years or older who had atrial high-rate episodes that lasted for at least 6 minutes and who had at least one additional risk factor for stroke.
Patients were randomly assigned in a 1:1 ratio to receive edoxaban or placebo. The primary efficacy outcome was a composite of cardiovascular death, stroke, or systemic embolism, evaluated in a time-to-event analysis. The safety outcome was a composite of death from any cause or major bleeding.
The mean age of the patients was 78 years, 37.4% were women, and the median duration of atrial high-rate episodes was 2.8 hours. The trial was terminated early, at a median follow-up of 21 months, on the basis of safety concerns and the results of an independent, informal assessment of futility for the efficacy of edoxaban; at termination, the planned enrollment had been completed.
Results showed that a primary efficacy outcome event occurred in 83 patients (3.2% per patient-year) in the edoxaban group and in 101 patients (4.0% per patient-year) in the placebo group (hazard ratio, 0.81; 95% confidence interval, 0.60-1.08; P = .15). The incidence of stroke was approximately 1% per patient-year in both groups.
A safety outcome event occurred in 149 patients (5.9% per patient-year) in the edoxaban group and in 114 patients (4.5% per patient-year) in the placebo group (HR, 1.31; 95% CI, 1.02-1.67; P = .03).
ECG-diagnosed AFib developed in 462 of 2,536 patients (18.2% total, 8.7% per patient-year).
In the NEJM article, the authors wrote that the findings of this trial – the low incidence of stroke that was not further reduced by treatment with edoxaban – may make it appropriate to withhold anticoagulant therapy for patients with atrial high-rate episodes.
The main difference between the population studied in this trial and patients with AFib, as documented on an ECG, appears to be the paucity and brevity of atrial arrhythmias in patients with atrial high-rate episodes (termed low arrhythmia burden). Published reports show that a low arrhythmia burden contributes to a low incidence of stroke among patients with AFib, the study authors wrote.
They added that the low rate of stroke in this trial suggests that in addition to clinical risk prediction formulas for stroke, methods to improve the estimation of stroke risk among patients with infrequent atrial arrhythmias detected by long-term monitoring are needed to guide decision-making on the use of anticoagulation.
Commenting on the NOAH-AFNET 6 results, the comoderator of the ESC HOTLINE session at which they were presented, Barbara Casadei, MD, John Radcliffe Hospital, Oxford, England, said: “Finally we know what to with these patients. Before we just had a variety of opinions with no evidence. I think that the trial really highlights that patients who come to the doctor with symptoms of AF[ib] or who have ECG-documented AF[ib] have a much higher risk of cardioembolic stroke than patients in whom this presumed AF[ib] is picked up incidentally from implanted devices.”
She added: “The stroke rates are very low in this trial, so anticoagulation was never going to work. But this is an important finding. We know that anticoagulants are not a free lunch. There is a significant bleeding risk. These results suggest that unless a patient has clinical AF[ib] that shows up on an ECG then we need to more cautious in prescribing anticoagulation.”
Also commenting on the study, immediate past president of the American College of Cardiology Ed Fry, MD, Ascension Indiana St. Vincent Heart Center, Indianapolis, said the management of patients with implanted cardiac devices or personal wearable technology that has picked up an abnormal rhythm suggestive of AFib was a big question in clinical practice.
“These episodes could be AF[ib], which comes with an increased stroke risk, but it could also be something else like atrial tachycardia or supraventricular tachycardia, which do not confer an increased stroke risk,” he explained.
“This study shows that without a firm diagnosis of AF[ib] on an ECG or some sort of continuous AF[ib] monitoring device, we are going to be anticoagulating people who don’t need it. They were exposed to the risk of bleeding without getting the benefit of a reduction in stroke risk,” Dr. Fry noted.
“The important outcome from this trial is that it gives comfort in we can be more confident in withholding anticoagulation until we get a firm diagnosis of AF[ib]. If we have a high index of suspicion that this could be AF[ib], then we can arrange for a further testing,” he added.
Second trial reporting soon
A trial similar to NOAH-AFNET 6 is currently underway – the ARTESIA trial, which is expected to be reported later in 2023.
“We are in close contact with the leadership of that trial, and we hope to do some meta-analysis,” Dr. Kirchhof said. “But I think today we’ve gone from no evidence to one outcome-based trial which shows there is no reason to use anticoagulation in these patients with atrial high-rate episodes. I think this is reason to change practice now, but yes, of course we need to look at the data in totality once the second trial has reported.”
But the lead investigator of the ARTESIA trial, Stuart Connolly, MD, McMaster University, Hamilton, Ont., does not believe the NOAH-AFNET 6 trial should change practice at this time.
“This trial fails to adequately address the critical issue that drives clinical decision-making in these patients because it is underpowered for the most important endpoint of stroke,” he said in an interview.
“The key question is whether anticoagulation reduces stroke in these patients,” he added. “To answer that, a clinical trial needs to have a lot of strokes, and this trial had very few. The trial was stopped early and had way too few strokes to properly answer this key question.”
The NOAH-AFNET 6 trial was an investigator-initiated trial funded by the German Center for Cardiovascular Research and Daiichi Sankyo Europe. Dr. Kirchhof reported research support from several drug and device companies active in AFib. He is also listed as an inventor on two patents held by the University of Hamburg on AFib therapy and AFib markers.
A version of this article first appeared on Medscape.com.
AMSTERDAM – Among patients with atrial high-rate episodes detected by implantable devices, anticoagulation with edoxaban did not significantly reduce the incidence of a composite outcome of cardiovascular death, stroke, or systemic embolism in comparison with placebo but was associated with a higher bleeding risk in the NOAH-AFNET 6 trial.
“ They do not need to be anticoagulated. That is a relief,” the lead investigator of the trial, Paulus Kirchhof, MD, University Heart and Vascular Center Hamburg (Germany), said in an interview.
Dr. Kirchhof pointed out that this result was unexpected. “Many of us thought that because atrial high-rate episodes look like AF[ib] when they occur, then they are an indication for anticoagulation. But based on these results from the first-ever randomized trial on this population, there is no need for anticoagulation in these patients.”
Dr. Kirchhof presented the NOAH-AFNET 6 trial at the annual congress of the European Society of Cardiology. The study was also simultaneously published in the New England Journal of Medicine.
The trial recruited patients with implanted devices that enable continuous monitoring of atrial rhythm, such as pacemakers and defibrillators. “Because we can record the rhythm day and night with these devices, they pick up small abnormalities. About 20% of these patients experience these occasional atrial high-rate episodes – short episodes that look like AF[ib], but they are rare and brief,” Dr. Kirchhof noted.
He explained that whether the occurrence of these atrial high-rate episodes in patients without AFib, as documented on a conventional electrocardiogram, justifies the initiation of anticoagulants has been unclear. “But this trial tells us that these episodes are different to AF[ib] that is diagnosed on ECG,” he added.
Another finding in the trial was that among these patients, there was an unexpectedly low rate of stroke, despite the patients’ having a CHADSVASC score of 4.
“Based on the result of this trial, these occasional atrial high-rate episodes do not appear to be associated with stroke. It appears quite benign,” Dr. Kirchhof said.
Implications for wearable technology?
He said the results may also have implications for wearable devices that pick up abnormal heart rhythm, such as smartwatches.
“We don’t know exactly what these wearable technologies are picking up, but most likely it is these atrial high-rate episodes. But we need more research on the value of these wearable technologies; we need randomized trials in this particular patient population before we consider anticoagulation in these patients,” Dr. Kirchhof stated.
The NOAH-AFNET 6 study was an event-driven, double-blind, double-dummy, randomized trial involving 2,536 patients aged 65 years or older who had atrial high-rate episodes that lasted for at least 6 minutes and who had at least one additional risk factor for stroke.
Patients were randomly assigned in a 1:1 ratio to receive edoxaban or placebo. The primary efficacy outcome was a composite of cardiovascular death, stroke, or systemic embolism, evaluated in a time-to-event analysis. The safety outcome was a composite of death from any cause or major bleeding.
The mean age of the patients was 78 years, 37.4% were women, and the median duration of atrial high-rate episodes was 2.8 hours. The trial was terminated early, at a median follow-up of 21 months, on the basis of safety concerns and the results of an independent, informal assessment of futility for the efficacy of edoxaban; at termination, the planned enrollment had been completed.
Results showed that a primary efficacy outcome event occurred in 83 patients (3.2% per patient-year) in the edoxaban group and in 101 patients (4.0% per patient-year) in the placebo group (hazard ratio, 0.81; 95% confidence interval, 0.60-1.08; P = .15). The incidence of stroke was approximately 1% per patient-year in both groups.
A safety outcome event occurred in 149 patients (5.9% per patient-year) in the edoxaban group and in 114 patients (4.5% per patient-year) in the placebo group (HR, 1.31; 95% CI, 1.02-1.67; P = .03).
ECG-diagnosed AFib developed in 462 of 2,536 patients (18.2% total, 8.7% per patient-year).
In the NEJM article, the authors wrote that the findings of this trial – the low incidence of stroke that was not further reduced by treatment with edoxaban – may make it appropriate to withhold anticoagulant therapy for patients with atrial high-rate episodes.
The main difference between the population studied in this trial and patients with AFib, as documented on an ECG, appears to be the paucity and brevity of atrial arrhythmias in patients with atrial high-rate episodes (termed low arrhythmia burden). Published reports show that a low arrhythmia burden contributes to a low incidence of stroke among patients with AFib, the study authors wrote.
They added that the low rate of stroke in this trial suggests that in addition to clinical risk prediction formulas for stroke, methods to improve the estimation of stroke risk among patients with infrequent atrial arrhythmias detected by long-term monitoring are needed to guide decision-making on the use of anticoagulation.
Commenting on the NOAH-AFNET 6 results, the comoderator of the ESC HOTLINE session at which they were presented, Barbara Casadei, MD, John Radcliffe Hospital, Oxford, England, said: “Finally we know what to with these patients. Before we just had a variety of opinions with no evidence. I think that the trial really highlights that patients who come to the doctor with symptoms of AF[ib] or who have ECG-documented AF[ib] have a much higher risk of cardioembolic stroke than patients in whom this presumed AF[ib] is picked up incidentally from implanted devices.”
She added: “The stroke rates are very low in this trial, so anticoagulation was never going to work. But this is an important finding. We know that anticoagulants are not a free lunch. There is a significant bleeding risk. These results suggest that unless a patient has clinical AF[ib] that shows up on an ECG then we need to more cautious in prescribing anticoagulation.”
Also commenting on the study, immediate past president of the American College of Cardiology Ed Fry, MD, Ascension Indiana St. Vincent Heart Center, Indianapolis, said the management of patients with implanted cardiac devices or personal wearable technology that has picked up an abnormal rhythm suggestive of AFib was a big question in clinical practice.
“These episodes could be AF[ib], which comes with an increased stroke risk, but it could also be something else like atrial tachycardia or supraventricular tachycardia, which do not confer an increased stroke risk,” he explained.
“This study shows that without a firm diagnosis of AF[ib] on an ECG or some sort of continuous AF[ib] monitoring device, we are going to be anticoagulating people who don’t need it. They were exposed to the risk of bleeding without getting the benefit of a reduction in stroke risk,” Dr. Fry noted.
“The important outcome from this trial is that it gives comfort in we can be more confident in withholding anticoagulation until we get a firm diagnosis of AF[ib]. If we have a high index of suspicion that this could be AF[ib], then we can arrange for a further testing,” he added.
Second trial reporting soon
A trial similar to NOAH-AFNET 6 is currently underway – the ARTESIA trial, which is expected to be reported later in 2023.
“We are in close contact with the leadership of that trial, and we hope to do some meta-analysis,” Dr. Kirchhof said. “But I think today we’ve gone from no evidence to one outcome-based trial which shows there is no reason to use anticoagulation in these patients with atrial high-rate episodes. I think this is reason to change practice now, but yes, of course we need to look at the data in totality once the second trial has reported.”
But the lead investigator of the ARTESIA trial, Stuart Connolly, MD, McMaster University, Hamilton, Ont., does not believe the NOAH-AFNET 6 trial should change practice at this time.
“This trial fails to adequately address the critical issue that drives clinical decision-making in these patients because it is underpowered for the most important endpoint of stroke,” he said in an interview.
“The key question is whether anticoagulation reduces stroke in these patients,” he added. “To answer that, a clinical trial needs to have a lot of strokes, and this trial had very few. The trial was stopped early and had way too few strokes to properly answer this key question.”
The NOAH-AFNET 6 trial was an investigator-initiated trial funded by the German Center for Cardiovascular Research and Daiichi Sankyo Europe. Dr. Kirchhof reported research support from several drug and device companies active in AFib. He is also listed as an inventor on two patents held by the University of Hamburg on AFib therapy and AFib markers.
A version of this article first appeared on Medscape.com.
AMSTERDAM – Among patients with atrial high-rate episodes detected by implantable devices, anticoagulation with edoxaban did not significantly reduce the incidence of a composite outcome of cardiovascular death, stroke, or systemic embolism in comparison with placebo but was associated with a higher bleeding risk in the NOAH-AFNET 6 trial.
“ They do not need to be anticoagulated. That is a relief,” the lead investigator of the trial, Paulus Kirchhof, MD, University Heart and Vascular Center Hamburg (Germany), said in an interview.
Dr. Kirchhof pointed out that this result was unexpected. “Many of us thought that because atrial high-rate episodes look like AF[ib] when they occur, then they are an indication for anticoagulation. But based on these results from the first-ever randomized trial on this population, there is no need for anticoagulation in these patients.”
Dr. Kirchhof presented the NOAH-AFNET 6 trial at the annual congress of the European Society of Cardiology. The study was also simultaneously published in the New England Journal of Medicine.
The trial recruited patients with implanted devices that enable continuous monitoring of atrial rhythm, such as pacemakers and defibrillators. “Because we can record the rhythm day and night with these devices, they pick up small abnormalities. About 20% of these patients experience these occasional atrial high-rate episodes – short episodes that look like AF[ib], but they are rare and brief,” Dr. Kirchhof noted.
He explained that whether the occurrence of these atrial high-rate episodes in patients without AFib, as documented on a conventional electrocardiogram, justifies the initiation of anticoagulants has been unclear. “But this trial tells us that these episodes are different to AF[ib] that is diagnosed on ECG,” he added.
Another finding in the trial was that among these patients, there was an unexpectedly low rate of stroke, despite the patients’ having a CHADSVASC score of 4.
“Based on the result of this trial, these occasional atrial high-rate episodes do not appear to be associated with stroke. It appears quite benign,” Dr. Kirchhof said.
Implications for wearable technology?
He said the results may also have implications for wearable devices that pick up abnormal heart rhythm, such as smartwatches.
“We don’t know exactly what these wearable technologies are picking up, but most likely it is these atrial high-rate episodes. But we need more research on the value of these wearable technologies; we need randomized trials in this particular patient population before we consider anticoagulation in these patients,” Dr. Kirchhof stated.
The NOAH-AFNET 6 study was an event-driven, double-blind, double-dummy, randomized trial involving 2,536 patients aged 65 years or older who had atrial high-rate episodes that lasted for at least 6 minutes and who had at least one additional risk factor for stroke.
Patients were randomly assigned in a 1:1 ratio to receive edoxaban or placebo. The primary efficacy outcome was a composite of cardiovascular death, stroke, or systemic embolism, evaluated in a time-to-event analysis. The safety outcome was a composite of death from any cause or major bleeding.
The mean age of the patients was 78 years, 37.4% were women, and the median duration of atrial high-rate episodes was 2.8 hours. The trial was terminated early, at a median follow-up of 21 months, on the basis of safety concerns and the results of an independent, informal assessment of futility for the efficacy of edoxaban; at termination, the planned enrollment had been completed.
Results showed that a primary efficacy outcome event occurred in 83 patients (3.2% per patient-year) in the edoxaban group and in 101 patients (4.0% per patient-year) in the placebo group (hazard ratio, 0.81; 95% confidence interval, 0.60-1.08; P = .15). The incidence of stroke was approximately 1% per patient-year in both groups.
A safety outcome event occurred in 149 patients (5.9% per patient-year) in the edoxaban group and in 114 patients (4.5% per patient-year) in the placebo group (HR, 1.31; 95% CI, 1.02-1.67; P = .03).
ECG-diagnosed AFib developed in 462 of 2,536 patients (18.2% total, 8.7% per patient-year).
In the NEJM article, the authors wrote that the findings of this trial – the low incidence of stroke that was not further reduced by treatment with edoxaban – may make it appropriate to withhold anticoagulant therapy for patients with atrial high-rate episodes.
The main difference between the population studied in this trial and patients with AFib, as documented on an ECG, appears to be the paucity and brevity of atrial arrhythmias in patients with atrial high-rate episodes (termed low arrhythmia burden). Published reports show that a low arrhythmia burden contributes to a low incidence of stroke among patients with AFib, the study authors wrote.
They added that the low rate of stroke in this trial suggests that in addition to clinical risk prediction formulas for stroke, methods to improve the estimation of stroke risk among patients with infrequent atrial arrhythmias detected by long-term monitoring are needed to guide decision-making on the use of anticoagulation.
Commenting on the NOAH-AFNET 6 results, the comoderator of the ESC HOTLINE session at which they were presented, Barbara Casadei, MD, John Radcliffe Hospital, Oxford, England, said: “Finally we know what to with these patients. Before we just had a variety of opinions with no evidence. I think that the trial really highlights that patients who come to the doctor with symptoms of AF[ib] or who have ECG-documented AF[ib] have a much higher risk of cardioembolic stroke than patients in whom this presumed AF[ib] is picked up incidentally from implanted devices.”
She added: “The stroke rates are very low in this trial, so anticoagulation was never going to work. But this is an important finding. We know that anticoagulants are not a free lunch. There is a significant bleeding risk. These results suggest that unless a patient has clinical AF[ib] that shows up on an ECG then we need to more cautious in prescribing anticoagulation.”
Also commenting on the study, immediate past president of the American College of Cardiology Ed Fry, MD, Ascension Indiana St. Vincent Heart Center, Indianapolis, said the management of patients with implanted cardiac devices or personal wearable technology that has picked up an abnormal rhythm suggestive of AFib was a big question in clinical practice.
“These episodes could be AF[ib], which comes with an increased stroke risk, but it could also be something else like atrial tachycardia or supraventricular tachycardia, which do not confer an increased stroke risk,” he explained.
“This study shows that without a firm diagnosis of AF[ib] on an ECG or some sort of continuous AF[ib] monitoring device, we are going to be anticoagulating people who don’t need it. They were exposed to the risk of bleeding without getting the benefit of a reduction in stroke risk,” Dr. Fry noted.
“The important outcome from this trial is that it gives comfort in we can be more confident in withholding anticoagulation until we get a firm diagnosis of AF[ib]. If we have a high index of suspicion that this could be AF[ib], then we can arrange for a further testing,” he added.
Second trial reporting soon
A trial similar to NOAH-AFNET 6 is currently underway – the ARTESIA trial, which is expected to be reported later in 2023.
“We are in close contact with the leadership of that trial, and we hope to do some meta-analysis,” Dr. Kirchhof said. “But I think today we’ve gone from no evidence to one outcome-based trial which shows there is no reason to use anticoagulation in these patients with atrial high-rate episodes. I think this is reason to change practice now, but yes, of course we need to look at the data in totality once the second trial has reported.”
But the lead investigator of the ARTESIA trial, Stuart Connolly, MD, McMaster University, Hamilton, Ont., does not believe the NOAH-AFNET 6 trial should change practice at this time.
“This trial fails to adequately address the critical issue that drives clinical decision-making in these patients because it is underpowered for the most important endpoint of stroke,” he said in an interview.
“The key question is whether anticoagulation reduces stroke in these patients,” he added. “To answer that, a clinical trial needs to have a lot of strokes, and this trial had very few. The trial was stopped early and had way too few strokes to properly answer this key question.”
The NOAH-AFNET 6 trial was an investigator-initiated trial funded by the German Center for Cardiovascular Research and Daiichi Sankyo Europe. Dr. Kirchhof reported research support from several drug and device companies active in AFib. He is also listed as an inventor on two patents held by the University of Hamburg on AFib therapy and AFib markers.
A version of this article first appeared on Medscape.com.
AT THE ESC CONGRESS 2023
Cardiac arrest centers no benefit in OHCA without STEMI
Survivors of out-of-hospital cardiac arrest (OHCA) without ST-segment elevation who were transported to the nearest hospital emergency department had outcomes similar to those of patients transported to specialist cardiac arrest centers, in the ARREST trial.
Both groups had the same 30-day survival, the primary outcome, as well as 3-month survival and neurologic outcomes.
senior author Simon R. Redwood, MD, principal investigator of ARREST, from Guy’s and St. Thomas’ NHS Trust Hospitals and King’s College, London, said during a press briefing. “These results may allow better resource allocation elsewhere.”
Importantly, this study excluded patients who clearly had myocardial infarction (MI), he stressed. Cardiac arrest can result from cardiac causes or from other events, including trauma, overdose, drowning, or electrocution, he noted.
On the other hand, patients with MI “will benefit from going straight to a heart attack center and having an attempt at reopening the artery,” he emphasized.
Tiffany Patterson, PhD, clinical lead of ARREST, with the same affiliations as Dr. Redwood, presented the trial findings at the annual congress of the European Society of Cardiology in Amsterdam, on Aug. 27. The study was simultaneously published online in The Lancet.
Observational studies of registry data suggest that postarrest care for patients resuscitated after cardiac arrest, without ST-segment elevation, may be best delivered in a specialized center, she noted.
The International Liaison Committee on Resuscitation called for a randomized clinical trial of patients resuscitated after cardiac arrest without ST-segment elevation to clarify this.
In the ARREST trial, among 800 patients with return of spontaneous circulation following OHCA without ST-segment elevation who were randomly assigned to be transported to specialized centers or an emergency department, there was no survival benefit, she summarized.
ARREST was “not simply a negative trial, but a new evidence-based starting point,” according to the trial discussant Lia Crotti, MD, PhD, IRCCS Istituto Auxologico Italiano and University Milano-Bicocca, Italy.
She drew attention to two findings: First, among the 862 patients who were enrolled, whom paramedics judged as being without an obvious noncardiac cause of the cardiac arrest, “only 60% ended up having a cardiac cause for their cardiac arrest and only around one quarter of the total had coronary artery disease.”
The small number of patients who could have benefited from early access to a catheterization laboratory probably contributed to the negative result obtained in this trial, with the loss of statistical power, she said.
Second, London is a dense urban area with high-quality acute care hospitals, so the standard of care in the nearest emergency department may be not so different from that in cardiac arrest centers, she noted. Furthermore, four of the seven cardiac arrest centers have an emergency department, and some of the standard care patients may have been transported there.
“If the clinical trial would be extended to the entire country, including rural areas, maybe the result would be different,” she said.
The study authors acknowledge that the main limitation of this study was that “it was done across London with a dense population in a small geographic area,” and “the London Ambulance Service has rapid response times and short transit times and delivers high quality prehospital care, which could limit generalizability.”
Asked during the press conference here why the results were so different from the registry study findings, Dr. Redwood said, “We’ve seen time and time again that registry data think they are telling us the answer. They’re actually not.”
The session cochairs, Rudolf de Boer, MD, PhD, of Erasmus University Medical Centre, Rotterdam, the Netherlands, and Faiez Zannad, MD, PhD, from University of Lorraine–Vandoeuvre-lès-Nancy, France, each congratulated the researchers on a well-done study.
Dr. de Boer wanted to know whether, for example, 100% of these resuscitated OHCA patients without ST-segment elevation had a cardiac cause, “Would results differ? Or is this just real life?” he asked. Dr. Patterson replied that the paramedics excluded obvious noncardiac causes and the findings were based on current facilities.
“Does this trial provide a definitive answer?” Dr. de Boer asked. Dr. Patterson replied that for the moment, subgroup analysis did not identify any subgroup that might benefit from expedited transport to a cardiac arrest center.
Dr. Zannad wanted to know how informed consent was obtained. Dr. Patterson noted that they have an excellent ethical committee that allowed them to undertake this research in vulnerable patients. Written informed consent was obtained from the patient once the initial emergency had passed if they had regained capacity.
Rationale and trial findings
“It’s very well established that early bystander CPR [cardiopulmonary resuscitation], early defibrillation, and advanced in-hospital care improves survival,” Dr. Redwood noted. “Despite this, only 1 in 10 survive to leave the hospital.”
Therefore, “a cardiac arrest center has been proposed as a way of improving outcome.” These centers have a catheterization laboratory, open 24 hours a day, 7 days a week, advanced critical care including advanced ventilation, temperature management of the patient, hemodynamic support, and neuroprognostication and rehab “because often these patients will have brain injury.
“There’s quite overwhelming registry data to suggest that these cardiac arrest centers improve outcome,” he said, “but these are limited by bias.”
Between January 2018 and December 2022, London Ambulance paramedics randomly assigned 862 patients who were successfully resuscitated and without a confirmed MI to be transported the nearest hospital emergency department or the catheterization laboratory in a cardiac arrest center.
Data were available for 822 participants. They had a mean age of 63 years, and 68% were male.
The primary endpoint, 30-day mortality, occurred in 258 (63%) of 411 participants in the cardiac arrest center group and in 258 (63%) of 412 in the standard care group (unadjusted risk ratio for survival, 1.00; 95% confidence interval [CI], 0.90-1.11; P = 0.96).
Mortality at 3 months was similar in both groups: 64% in the standard care group and 65% in the cardiac arrest center group.
Neurologic outcomes at discharge and 3 months were similar in both groups.
Eight (2%) of 414 patients in the cardiac arrest center group and three (1%) of 413 in the standard care group had serious adverse events, none of which were deemed related to the trial intervention.
A cardiac cause of arrest was identified in roughly 60% of patients in each group, and of these, roughly 42% were coronary causes, 33% were arrhythmia, and 17% were cardiomyopathy.
The median time from cardiac arrest to hospital arrival was 84 minutes in the cardiac arrest center group and 77 minutes in the standard care group.
“Surprising and important RCT evidence”
In an accompanying editorial, Carolina Malta Hansen, MD, PhD, University of Copenhagen, and colleagues wrote that “this study provides randomized trial evidence that in urban settings such as London, there is no survival advantage of a strategy of transporting patients who have been resuscitated to centres with specialty expertise in care of cardiac arrest.
“This result is surprising and important, since this complex and critically ill population would be expected to benefit from centres with more expertise.”
However, “it would be a mistake to conclude that the trial results apply to regions where local hospitals provide a lower quality of care than those in this trial,” they cautioned.
“Where does this leave the medical community, researchers, and society in general?” they asked rhetorically. “Prioritising a minimum standard of care at local hospitals caring for this population is at least as important as ensuring high-quality care or advanced treatment at tertiary centres.
“This trial also calls for more focus on the basics, including efforts to increase bystander cardiopulmonary resuscitation and early defibrillation, aspects of care that are currently being assessed in two ongoing clinical trials (NCT04660526 and NCT03835403) and are most strongly associated with improved survival, when coupled with high-quality prehospital care with trained staff and short response times,” they concluded.
The study was fully funded by the British Heart Foundation. The authors reported that they have no relevant financial disclosures. The financial disclosures of the editorialists are listed with the editorial.
A version of this article first appeared on Medscape.com.
Survivors of out-of-hospital cardiac arrest (OHCA) without ST-segment elevation who were transported to the nearest hospital emergency department had outcomes similar to those of patients transported to specialist cardiac arrest centers, in the ARREST trial.
Both groups had the same 30-day survival, the primary outcome, as well as 3-month survival and neurologic outcomes.
senior author Simon R. Redwood, MD, principal investigator of ARREST, from Guy’s and St. Thomas’ NHS Trust Hospitals and King’s College, London, said during a press briefing. “These results may allow better resource allocation elsewhere.”
Importantly, this study excluded patients who clearly had myocardial infarction (MI), he stressed. Cardiac arrest can result from cardiac causes or from other events, including trauma, overdose, drowning, or electrocution, he noted.
On the other hand, patients with MI “will benefit from going straight to a heart attack center and having an attempt at reopening the artery,” he emphasized.
Tiffany Patterson, PhD, clinical lead of ARREST, with the same affiliations as Dr. Redwood, presented the trial findings at the annual congress of the European Society of Cardiology in Amsterdam, on Aug. 27. The study was simultaneously published online in The Lancet.
Observational studies of registry data suggest that postarrest care for patients resuscitated after cardiac arrest, without ST-segment elevation, may be best delivered in a specialized center, she noted.
The International Liaison Committee on Resuscitation called for a randomized clinical trial of patients resuscitated after cardiac arrest without ST-segment elevation to clarify this.
In the ARREST trial, among 800 patients with return of spontaneous circulation following OHCA without ST-segment elevation who were randomly assigned to be transported to specialized centers or an emergency department, there was no survival benefit, she summarized.
ARREST was “not simply a negative trial, but a new evidence-based starting point,” according to the trial discussant Lia Crotti, MD, PhD, IRCCS Istituto Auxologico Italiano and University Milano-Bicocca, Italy.
She drew attention to two findings: First, among the 862 patients who were enrolled, whom paramedics judged as being without an obvious noncardiac cause of the cardiac arrest, “only 60% ended up having a cardiac cause for their cardiac arrest and only around one quarter of the total had coronary artery disease.”
The small number of patients who could have benefited from early access to a catheterization laboratory probably contributed to the negative result obtained in this trial, with the loss of statistical power, she said.
Second, London is a dense urban area with high-quality acute care hospitals, so the standard of care in the nearest emergency department may be not so different from that in cardiac arrest centers, she noted. Furthermore, four of the seven cardiac arrest centers have an emergency department, and some of the standard care patients may have been transported there.
“If the clinical trial would be extended to the entire country, including rural areas, maybe the result would be different,” she said.
The study authors acknowledge that the main limitation of this study was that “it was done across London with a dense population in a small geographic area,” and “the London Ambulance Service has rapid response times and short transit times and delivers high quality prehospital care, which could limit generalizability.”
Asked during the press conference here why the results were so different from the registry study findings, Dr. Redwood said, “We’ve seen time and time again that registry data think they are telling us the answer. They’re actually not.”
The session cochairs, Rudolf de Boer, MD, PhD, of Erasmus University Medical Centre, Rotterdam, the Netherlands, and Faiez Zannad, MD, PhD, from University of Lorraine–Vandoeuvre-lès-Nancy, France, each congratulated the researchers on a well-done study.
Dr. de Boer wanted to know whether, for example, 100% of these resuscitated OHCA patients without ST-segment elevation had a cardiac cause, “Would results differ? Or is this just real life?” he asked. Dr. Patterson replied that the paramedics excluded obvious noncardiac causes and the findings were based on current facilities.
“Does this trial provide a definitive answer?” Dr. de Boer asked. Dr. Patterson replied that for the moment, subgroup analysis did not identify any subgroup that might benefit from expedited transport to a cardiac arrest center.
Dr. Zannad wanted to know how informed consent was obtained. Dr. Patterson noted that they have an excellent ethical committee that allowed them to undertake this research in vulnerable patients. Written informed consent was obtained from the patient once the initial emergency had passed if they had regained capacity.
Rationale and trial findings
“It’s very well established that early bystander CPR [cardiopulmonary resuscitation], early defibrillation, and advanced in-hospital care improves survival,” Dr. Redwood noted. “Despite this, only 1 in 10 survive to leave the hospital.”
Therefore, “a cardiac arrest center has been proposed as a way of improving outcome.” These centers have a catheterization laboratory, open 24 hours a day, 7 days a week, advanced critical care including advanced ventilation, temperature management of the patient, hemodynamic support, and neuroprognostication and rehab “because often these patients will have brain injury.
“There’s quite overwhelming registry data to suggest that these cardiac arrest centers improve outcome,” he said, “but these are limited by bias.”
Between January 2018 and December 2022, London Ambulance paramedics randomly assigned 862 patients who were successfully resuscitated and without a confirmed MI to be transported the nearest hospital emergency department or the catheterization laboratory in a cardiac arrest center.
Data were available for 822 participants. They had a mean age of 63 years, and 68% were male.
The primary endpoint, 30-day mortality, occurred in 258 (63%) of 411 participants in the cardiac arrest center group and in 258 (63%) of 412 in the standard care group (unadjusted risk ratio for survival, 1.00; 95% confidence interval [CI], 0.90-1.11; P = 0.96).
Mortality at 3 months was similar in both groups: 64% in the standard care group and 65% in the cardiac arrest center group.
Neurologic outcomes at discharge and 3 months were similar in both groups.
Eight (2%) of 414 patients in the cardiac arrest center group and three (1%) of 413 in the standard care group had serious adverse events, none of which were deemed related to the trial intervention.
A cardiac cause of arrest was identified in roughly 60% of patients in each group, and of these, roughly 42% were coronary causes, 33% were arrhythmia, and 17% were cardiomyopathy.
The median time from cardiac arrest to hospital arrival was 84 minutes in the cardiac arrest center group and 77 minutes in the standard care group.
“Surprising and important RCT evidence”
In an accompanying editorial, Carolina Malta Hansen, MD, PhD, University of Copenhagen, and colleagues wrote that “this study provides randomized trial evidence that in urban settings such as London, there is no survival advantage of a strategy of transporting patients who have been resuscitated to centres with specialty expertise in care of cardiac arrest.
“This result is surprising and important, since this complex and critically ill population would be expected to benefit from centres with more expertise.”
However, “it would be a mistake to conclude that the trial results apply to regions where local hospitals provide a lower quality of care than those in this trial,” they cautioned.
“Where does this leave the medical community, researchers, and society in general?” they asked rhetorically. “Prioritising a minimum standard of care at local hospitals caring for this population is at least as important as ensuring high-quality care or advanced treatment at tertiary centres.
“This trial also calls for more focus on the basics, including efforts to increase bystander cardiopulmonary resuscitation and early defibrillation, aspects of care that are currently being assessed in two ongoing clinical trials (NCT04660526 and NCT03835403) and are most strongly associated with improved survival, when coupled with high-quality prehospital care with trained staff and short response times,” they concluded.
The study was fully funded by the British Heart Foundation. The authors reported that they have no relevant financial disclosures. The financial disclosures of the editorialists are listed with the editorial.
A version of this article first appeared on Medscape.com.
Survivors of out-of-hospital cardiac arrest (OHCA) without ST-segment elevation who were transported to the nearest hospital emergency department had outcomes similar to those of patients transported to specialist cardiac arrest centers, in the ARREST trial.
Both groups had the same 30-day survival, the primary outcome, as well as 3-month survival and neurologic outcomes.
senior author Simon R. Redwood, MD, principal investigator of ARREST, from Guy’s and St. Thomas’ NHS Trust Hospitals and King’s College, London, said during a press briefing. “These results may allow better resource allocation elsewhere.”
Importantly, this study excluded patients who clearly had myocardial infarction (MI), he stressed. Cardiac arrest can result from cardiac causes or from other events, including trauma, overdose, drowning, or electrocution, he noted.
On the other hand, patients with MI “will benefit from going straight to a heart attack center and having an attempt at reopening the artery,” he emphasized.
Tiffany Patterson, PhD, clinical lead of ARREST, with the same affiliations as Dr. Redwood, presented the trial findings at the annual congress of the European Society of Cardiology in Amsterdam, on Aug. 27. The study was simultaneously published online in The Lancet.
Observational studies of registry data suggest that postarrest care for patients resuscitated after cardiac arrest, without ST-segment elevation, may be best delivered in a specialized center, she noted.
The International Liaison Committee on Resuscitation called for a randomized clinical trial of patients resuscitated after cardiac arrest without ST-segment elevation to clarify this.
In the ARREST trial, among 800 patients with return of spontaneous circulation following OHCA without ST-segment elevation who were randomly assigned to be transported to specialized centers or an emergency department, there was no survival benefit, she summarized.
ARREST was “not simply a negative trial, but a new evidence-based starting point,” according to the trial discussant Lia Crotti, MD, PhD, IRCCS Istituto Auxologico Italiano and University Milano-Bicocca, Italy.
She drew attention to two findings: First, among the 862 patients who were enrolled, whom paramedics judged as being without an obvious noncardiac cause of the cardiac arrest, “only 60% ended up having a cardiac cause for their cardiac arrest and only around one quarter of the total had coronary artery disease.”
The small number of patients who could have benefited from early access to a catheterization laboratory probably contributed to the negative result obtained in this trial, with the loss of statistical power, she said.
Second, London is a dense urban area with high-quality acute care hospitals, so the standard of care in the nearest emergency department may be not so different from that in cardiac arrest centers, she noted. Furthermore, four of the seven cardiac arrest centers have an emergency department, and some of the standard care patients may have been transported there.
“If the clinical trial would be extended to the entire country, including rural areas, maybe the result would be different,” she said.
The study authors acknowledge that the main limitation of this study was that “it was done across London with a dense population in a small geographic area,” and “the London Ambulance Service has rapid response times and short transit times and delivers high quality prehospital care, which could limit generalizability.”
Asked during the press conference here why the results were so different from the registry study findings, Dr. Redwood said, “We’ve seen time and time again that registry data think they are telling us the answer. They’re actually not.”
The session cochairs, Rudolf de Boer, MD, PhD, of Erasmus University Medical Centre, Rotterdam, the Netherlands, and Faiez Zannad, MD, PhD, from University of Lorraine–Vandoeuvre-lès-Nancy, France, each congratulated the researchers on a well-done study.
Dr. de Boer wanted to know whether, for example, 100% of these resuscitated OHCA patients without ST-segment elevation had a cardiac cause, “Would results differ? Or is this just real life?” he asked. Dr. Patterson replied that the paramedics excluded obvious noncardiac causes and the findings were based on current facilities.
“Does this trial provide a definitive answer?” Dr. de Boer asked. Dr. Patterson replied that for the moment, subgroup analysis did not identify any subgroup that might benefit from expedited transport to a cardiac arrest center.
Dr. Zannad wanted to know how informed consent was obtained. Dr. Patterson noted that they have an excellent ethical committee that allowed them to undertake this research in vulnerable patients. Written informed consent was obtained from the patient once the initial emergency had passed if they had regained capacity.
Rationale and trial findings
“It’s very well established that early bystander CPR [cardiopulmonary resuscitation], early defibrillation, and advanced in-hospital care improves survival,” Dr. Redwood noted. “Despite this, only 1 in 10 survive to leave the hospital.”
Therefore, “a cardiac arrest center has been proposed as a way of improving outcome.” These centers have a catheterization laboratory, open 24 hours a day, 7 days a week, advanced critical care including advanced ventilation, temperature management of the patient, hemodynamic support, and neuroprognostication and rehab “because often these patients will have brain injury.
“There’s quite overwhelming registry data to suggest that these cardiac arrest centers improve outcome,” he said, “but these are limited by bias.”
Between January 2018 and December 2022, London Ambulance paramedics randomly assigned 862 patients who were successfully resuscitated and without a confirmed MI to be transported the nearest hospital emergency department or the catheterization laboratory in a cardiac arrest center.
Data were available for 822 participants. They had a mean age of 63 years, and 68% were male.
The primary endpoint, 30-day mortality, occurred in 258 (63%) of 411 participants in the cardiac arrest center group and in 258 (63%) of 412 in the standard care group (unadjusted risk ratio for survival, 1.00; 95% confidence interval [CI], 0.90-1.11; P = 0.96).
Mortality at 3 months was similar in both groups: 64% in the standard care group and 65% in the cardiac arrest center group.
Neurologic outcomes at discharge and 3 months were similar in both groups.
Eight (2%) of 414 patients in the cardiac arrest center group and three (1%) of 413 in the standard care group had serious adverse events, none of which were deemed related to the trial intervention.
A cardiac cause of arrest was identified in roughly 60% of patients in each group, and of these, roughly 42% were coronary causes, 33% were arrhythmia, and 17% were cardiomyopathy.
The median time from cardiac arrest to hospital arrival was 84 minutes in the cardiac arrest center group and 77 minutes in the standard care group.
“Surprising and important RCT evidence”
In an accompanying editorial, Carolina Malta Hansen, MD, PhD, University of Copenhagen, and colleagues wrote that “this study provides randomized trial evidence that in urban settings such as London, there is no survival advantage of a strategy of transporting patients who have been resuscitated to centres with specialty expertise in care of cardiac arrest.
“This result is surprising and important, since this complex and critically ill population would be expected to benefit from centres with more expertise.”
However, “it would be a mistake to conclude that the trial results apply to regions where local hospitals provide a lower quality of care than those in this trial,” they cautioned.
“Where does this leave the medical community, researchers, and society in general?” they asked rhetorically. “Prioritising a minimum standard of care at local hospitals caring for this population is at least as important as ensuring high-quality care or advanced treatment at tertiary centres.
“This trial also calls for more focus on the basics, including efforts to increase bystander cardiopulmonary resuscitation and early defibrillation, aspects of care that are currently being assessed in two ongoing clinical trials (NCT04660526 and NCT03835403) and are most strongly associated with improved survival, when coupled with high-quality prehospital care with trained staff and short response times,” they concluded.
The study was fully funded by the British Heart Foundation. The authors reported that they have no relevant financial disclosures. The financial disclosures of the editorialists are listed with the editorial.
A version of this article first appeared on Medscape.com.
FROM THE ESC CONGRESS 2023
ESC backs SGLT2 inhibitor plus GLP-1 in diabetes with high CVD risk
AMSTERDAM – The era of guidelines that recommended treatment with either a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or a glucagonlike peptide-1 (GLP-1) receptor agonist in people with type 2 diabetes mellitus and established cardiovascular disease (CVD) ended with new recommendations from the European Society of Cardiology that call for starting both classes simultaneously.
said Darren K. McGuire, MD, at the annual congress of the European Society of Cardiology.
The society’s new guidelines for managing CVD in patients with diabetes, released on Aug. 25 and presented in several sessions at the Congress, also break with the past by calling for starting treatment with both an SGLT-2 inhibitor and a GLP-1 receptor agonist without regard to a person’s existing level of glucose control, including their current and target hemoglobin A1c levels, and regardless of background therapy, added Dr. McGuire, a cardiologist and professor at the UT Southwestern Medical Center in Dallas and a member of the ESC panel that wrote the new guidelines.
Instead, the new guidance calls for starting both drug classes promptly in people diagnosed with type 2 diabetes and established atherosclerotic CVD.
Both the previous ESC guidelines from 2019 as well as the current Standards of Care for 2023 document from the American Diabetes Association call for using one class or the other, but they hedge on combined treatment as discretionary.
Different mechanisms mean additive benefits
“With increasing numbers of patients with type 2 diabetes in trials for SGLT-2 inhibitors or GLP-1 receptor agonists who were also on the other drug class, we’ve done large, stratified analyses that suggest no treatment-effect modification” when people received agents from both drug classes, Dr. McGuire explained in an interview. “While we don’t understand the mechanisms of action of these drugs for CVD, we’ve become very confident that they use different mechanisms” that appear to have at least partially additive effects.
“Their benefits for CVD risk reduction are completely independent of their glucose effects. They are cardiology drugs,” Dr. McGuire added.
The new ESC guidelines highlight two other clinical settings where people with type 2 diabetes should receive an SGLT-2 inhibitor regardless of their existing level of glucose control and any other medical treatment: people with heart failure and people with chronic kidney disease (CKD) based on a depressed estimated glomerular filtration rate and an elevated urine albumin-to-creatinine ratio.
Nephropathy was considered by the ESC’s guideline panel to confer risk that is similar to that of established atherosclerotic CVD, Dr. McGuire said.
The guidelines also, for the first time for ESC recommendations, made treatment with finerenone (Kerendia, Bayer) a class 1 level A recommendation for people with type 2 diabetes and CKD.
SCORE2-Diabetes risk estimator
Another major change in the new ESC guideline revision is introduction of a CVD risk calculator intended to estimate the risk among people with type 2 diabetes but without established CVD, heart failure, or CKD.
Called the SCORE2-Diabetes risk estimator, it calculates a person’s 10-year risk for CVD and includes adjustment based on the European region where a person lives; it also tallies different risk levels for women and for men.
The researchers who developed the SCORE2-Diabetes calculator used data from nearly 230,000 people to devise the tool and then validated it with data from an additional 217,000 Europeans with type 2 diabetes.
Key features of the calculator include its use of routinely collected clinical values, such as age, sex, systolic blood pressure, smoking status, serum cholesterol levels, age at diabetes diagnosis, hemoglobin A1c level, and estimated glomerular filtration rate.
“For the first time we have a clear score to categorize risk” in people with type 2 diabetes and identify who needs more aggressive treatment to prevent CVD development,” said Emanuele Di Angelantonio, MD, PhD, deputy director of the cardiovascular epidemiology unit at the University of Cambridge (England).
The guidelines say that people who have a low (< 5%) or moderate (5%-9%) 10-year risk for CVD are possible candidates for metformin treatment. Those with high (10%-19%) or very high (≥ 20%) risk are possible candidates for treatment with metformin and/or an SGLT-2 inhibitor and/or a GLP-1 receptor agonist, said Dr. Di Angelantonio during his talk at the congress on the new risk score.
“The risk score is a good addition” because it estimates future CVD risk better and more systematically than usual practice, which generally relies on no systematic tool, said Naveed Sattar, PhD, professor of metabolic medicine at the University of Glasgow (Scotland) and also a member of the guideline-writing panel.
The new risk score “is a reasonable way” to identify people without CVD but at elevated risk who might benefit from treatment with a relatively expensive drug, such as an SGLT-2 inhibitor, Dr. Sattar said in an interview. “It doesn’t rely on any fancy biomarkers or imaging, and it takes about 30 seconds to calculate. It’s not perfect, but it gets the job done,” and it will increase the number of people with type 2 diabetes who will receive an SGLT-2 inhibitor, he predicted.
Dr. McGuire has been a consultant to Altimmune, Applied Therapeutics, AstraZeneca, Bayer, Boehringer-Ingelheim, Intercept, Lexion, Lilly, Merck, New Amsterdam, and Pfizer. Dr. Di Angelantonio had no disclosures. Dr. Sattar has been a consultant to Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk, Pfizer, and Roche Diagnostics.
A version of this article appeared on Medscape.com.
AMSTERDAM – The era of guidelines that recommended treatment with either a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or a glucagonlike peptide-1 (GLP-1) receptor agonist in people with type 2 diabetes mellitus and established cardiovascular disease (CVD) ended with new recommendations from the European Society of Cardiology that call for starting both classes simultaneously.
said Darren K. McGuire, MD, at the annual congress of the European Society of Cardiology.
The society’s new guidelines for managing CVD in patients with diabetes, released on Aug. 25 and presented in several sessions at the Congress, also break with the past by calling for starting treatment with both an SGLT-2 inhibitor and a GLP-1 receptor agonist without regard to a person’s existing level of glucose control, including their current and target hemoglobin A1c levels, and regardless of background therapy, added Dr. McGuire, a cardiologist and professor at the UT Southwestern Medical Center in Dallas and a member of the ESC panel that wrote the new guidelines.
Instead, the new guidance calls for starting both drug classes promptly in people diagnosed with type 2 diabetes and established atherosclerotic CVD.
Both the previous ESC guidelines from 2019 as well as the current Standards of Care for 2023 document from the American Diabetes Association call for using one class or the other, but they hedge on combined treatment as discretionary.
Different mechanisms mean additive benefits
“With increasing numbers of patients with type 2 diabetes in trials for SGLT-2 inhibitors or GLP-1 receptor agonists who were also on the other drug class, we’ve done large, stratified analyses that suggest no treatment-effect modification” when people received agents from both drug classes, Dr. McGuire explained in an interview. “While we don’t understand the mechanisms of action of these drugs for CVD, we’ve become very confident that they use different mechanisms” that appear to have at least partially additive effects.
“Their benefits for CVD risk reduction are completely independent of their glucose effects. They are cardiology drugs,” Dr. McGuire added.
The new ESC guidelines highlight two other clinical settings where people with type 2 diabetes should receive an SGLT-2 inhibitor regardless of their existing level of glucose control and any other medical treatment: people with heart failure and people with chronic kidney disease (CKD) based on a depressed estimated glomerular filtration rate and an elevated urine albumin-to-creatinine ratio.
Nephropathy was considered by the ESC’s guideline panel to confer risk that is similar to that of established atherosclerotic CVD, Dr. McGuire said.
The guidelines also, for the first time for ESC recommendations, made treatment with finerenone (Kerendia, Bayer) a class 1 level A recommendation for people with type 2 diabetes and CKD.
SCORE2-Diabetes risk estimator
Another major change in the new ESC guideline revision is introduction of a CVD risk calculator intended to estimate the risk among people with type 2 diabetes but without established CVD, heart failure, or CKD.
Called the SCORE2-Diabetes risk estimator, it calculates a person’s 10-year risk for CVD and includes adjustment based on the European region where a person lives; it also tallies different risk levels for women and for men.
The researchers who developed the SCORE2-Diabetes calculator used data from nearly 230,000 people to devise the tool and then validated it with data from an additional 217,000 Europeans with type 2 diabetes.
Key features of the calculator include its use of routinely collected clinical values, such as age, sex, systolic blood pressure, smoking status, serum cholesterol levels, age at diabetes diagnosis, hemoglobin A1c level, and estimated glomerular filtration rate.
“For the first time we have a clear score to categorize risk” in people with type 2 diabetes and identify who needs more aggressive treatment to prevent CVD development,” said Emanuele Di Angelantonio, MD, PhD, deputy director of the cardiovascular epidemiology unit at the University of Cambridge (England).
The guidelines say that people who have a low (< 5%) or moderate (5%-9%) 10-year risk for CVD are possible candidates for metformin treatment. Those with high (10%-19%) or very high (≥ 20%) risk are possible candidates for treatment with metformin and/or an SGLT-2 inhibitor and/or a GLP-1 receptor agonist, said Dr. Di Angelantonio during his talk at the congress on the new risk score.
“The risk score is a good addition” because it estimates future CVD risk better and more systematically than usual practice, which generally relies on no systematic tool, said Naveed Sattar, PhD, professor of metabolic medicine at the University of Glasgow (Scotland) and also a member of the guideline-writing panel.
The new risk score “is a reasonable way” to identify people without CVD but at elevated risk who might benefit from treatment with a relatively expensive drug, such as an SGLT-2 inhibitor, Dr. Sattar said in an interview. “It doesn’t rely on any fancy biomarkers or imaging, and it takes about 30 seconds to calculate. It’s not perfect, but it gets the job done,” and it will increase the number of people with type 2 diabetes who will receive an SGLT-2 inhibitor, he predicted.
Dr. McGuire has been a consultant to Altimmune, Applied Therapeutics, AstraZeneca, Bayer, Boehringer-Ingelheim, Intercept, Lexion, Lilly, Merck, New Amsterdam, and Pfizer. Dr. Di Angelantonio had no disclosures. Dr. Sattar has been a consultant to Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk, Pfizer, and Roche Diagnostics.
A version of this article appeared on Medscape.com.
AMSTERDAM – The era of guidelines that recommended treatment with either a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or a glucagonlike peptide-1 (GLP-1) receptor agonist in people with type 2 diabetes mellitus and established cardiovascular disease (CVD) ended with new recommendations from the European Society of Cardiology that call for starting both classes simultaneously.
said Darren K. McGuire, MD, at the annual congress of the European Society of Cardiology.
The society’s new guidelines for managing CVD in patients with diabetes, released on Aug. 25 and presented in several sessions at the Congress, also break with the past by calling for starting treatment with both an SGLT-2 inhibitor and a GLP-1 receptor agonist without regard to a person’s existing level of glucose control, including their current and target hemoglobin A1c levels, and regardless of background therapy, added Dr. McGuire, a cardiologist and professor at the UT Southwestern Medical Center in Dallas and a member of the ESC panel that wrote the new guidelines.
Instead, the new guidance calls for starting both drug classes promptly in people diagnosed with type 2 diabetes and established atherosclerotic CVD.
Both the previous ESC guidelines from 2019 as well as the current Standards of Care for 2023 document from the American Diabetes Association call for using one class or the other, but they hedge on combined treatment as discretionary.
Different mechanisms mean additive benefits
“With increasing numbers of patients with type 2 diabetes in trials for SGLT-2 inhibitors or GLP-1 receptor agonists who were also on the other drug class, we’ve done large, stratified analyses that suggest no treatment-effect modification” when people received agents from both drug classes, Dr. McGuire explained in an interview. “While we don’t understand the mechanisms of action of these drugs for CVD, we’ve become very confident that they use different mechanisms” that appear to have at least partially additive effects.
“Their benefits for CVD risk reduction are completely independent of their glucose effects. They are cardiology drugs,” Dr. McGuire added.
The new ESC guidelines highlight two other clinical settings where people with type 2 diabetes should receive an SGLT-2 inhibitor regardless of their existing level of glucose control and any other medical treatment: people with heart failure and people with chronic kidney disease (CKD) based on a depressed estimated glomerular filtration rate and an elevated urine albumin-to-creatinine ratio.
Nephropathy was considered by the ESC’s guideline panel to confer risk that is similar to that of established atherosclerotic CVD, Dr. McGuire said.
The guidelines also, for the first time for ESC recommendations, made treatment with finerenone (Kerendia, Bayer) a class 1 level A recommendation for people with type 2 diabetes and CKD.
SCORE2-Diabetes risk estimator
Another major change in the new ESC guideline revision is introduction of a CVD risk calculator intended to estimate the risk among people with type 2 diabetes but without established CVD, heart failure, or CKD.
Called the SCORE2-Diabetes risk estimator, it calculates a person’s 10-year risk for CVD and includes adjustment based on the European region where a person lives; it also tallies different risk levels for women and for men.
The researchers who developed the SCORE2-Diabetes calculator used data from nearly 230,000 people to devise the tool and then validated it with data from an additional 217,000 Europeans with type 2 diabetes.
Key features of the calculator include its use of routinely collected clinical values, such as age, sex, systolic blood pressure, smoking status, serum cholesterol levels, age at diabetes diagnosis, hemoglobin A1c level, and estimated glomerular filtration rate.
“For the first time we have a clear score to categorize risk” in people with type 2 diabetes and identify who needs more aggressive treatment to prevent CVD development,” said Emanuele Di Angelantonio, MD, PhD, deputy director of the cardiovascular epidemiology unit at the University of Cambridge (England).
The guidelines say that people who have a low (< 5%) or moderate (5%-9%) 10-year risk for CVD are possible candidates for metformin treatment. Those with high (10%-19%) or very high (≥ 20%) risk are possible candidates for treatment with metformin and/or an SGLT-2 inhibitor and/or a GLP-1 receptor agonist, said Dr. Di Angelantonio during his talk at the congress on the new risk score.
“The risk score is a good addition” because it estimates future CVD risk better and more systematically than usual practice, which generally relies on no systematic tool, said Naveed Sattar, PhD, professor of metabolic medicine at the University of Glasgow (Scotland) and also a member of the guideline-writing panel.
The new risk score “is a reasonable way” to identify people without CVD but at elevated risk who might benefit from treatment with a relatively expensive drug, such as an SGLT-2 inhibitor, Dr. Sattar said in an interview. “It doesn’t rely on any fancy biomarkers or imaging, and it takes about 30 seconds to calculate. It’s not perfect, but it gets the job done,” and it will increase the number of people with type 2 diabetes who will receive an SGLT-2 inhibitor, he predicted.
Dr. McGuire has been a consultant to Altimmune, Applied Therapeutics, AstraZeneca, Bayer, Boehringer-Ingelheim, Intercept, Lexion, Lilly, Merck, New Amsterdam, and Pfizer. Dr. Di Angelantonio had no disclosures. Dr. Sattar has been a consultant to Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk, Pfizer, and Roche Diagnostics.
A version of this article appeared on Medscape.com.
AT ESC CONGRESS 2023
ECMO for shock in acute MI won’t help, may harm: ECLS-SHOCK
Patients with acute myocardial infarction (MI) and shock are often put on extracorporeal membrane oxygenation (ECMO) support before heading to the catheterization laboratory. But the practice, done routinely, doesn’t have much backing from randomized trials. Now it’s being challenged by one of the largest such studies to explore the issue.
ECMO-managed patients, moreover, had sharply increased risks for moderate and severe bleeding and vascular complications.
A challenge to common practice
The results undercut guidelines that promote mechanical circulatory support in MI-related cardiogenic shock primarily based on observational data, and they argue against what’s become common practice, said Holger Thiele, MD, Heart Center Leipzig, University of Leipzig, Germany.
Such use of ECMO could well offer some type of advantage in MI-related shock, but the data so far don’t show it, Dr. Thiele said at a press conference on the new study, called ECLS-SHOCK, at the annual congress of the European Society of Cardiology in Amsterdam. He formally presented the trial at the meeting and is lead author on its simultaneous publication in The New England Journal of Medicine.
Almost half of the trial’s patients died, whether or not they had been put on ECMO. All-cause mortality at 30 days, the primary endpoint, was about the same, at 47.8% and 49.0% for the ECMO and usual-care groups, respectively.
Meanwhile, Dr. Thiele reported, risks for moderate or severe bleeding more than doubled and serious peripheral vascular complications almost tripled with addition of ECMO support.
The findings, he noted, are consistent with a new meta-analysis of trials testing ECMO in MI-related shock that also showed increases in bleeding with survival gains using the devices. Dr. Thiele is senior author on that report, published in The Lancet to coincide with his ECLS-SHOCK presentation.
Would any subgroups benefit?
Importantly, he said in an interview, ECMO’s failure to improve 30-day survival in the trial probably applies across the spectrum of patients with MI-related shock. Subgroup analyses in both ECLS-SHOCK and the meta-analysis didn’t identify any groups that benefit, Dr. Thiele observed.
For example, there were no significant differences for the primary outcome by age, sex, whether the MI was ST-segment elevation MI or non–ST-segment elevation MI or anterior or nonanterior, or whether the patient had diabetes.
If there is a subgroup in MI-related shock that is likely to benefit from the intervention with lower mortality, he said, “it’s less than 1%, if you ask me.”
An accompanying editorial essentially agreed, arguing that ECLS-SHOCK contests the intervention’s broad application in MI-related shock without shedding light on any selective benefits.
“Will the results of the ECLS-SHOCK trial change current clinical practice? If the goal of [ECMO] is to improve 30-day mortality, these data should steer interventional and critical care cardiologists away from its early routine implementation for all or even most patients with myocardial infarction and cardiogenic shock,” the editorialists say.
“There will be some patients in this population for whom [ECMO] is necessary and lifesaving, but the results of the ECLS-SHOCK trial do not tell us which ones,” write Jane A. Leopold, MD, Brigham and Women’s Hospital, Boston, and Darren B. Taichman, MD, PhD, Penn Presbyterian Medical Center, Philadelphia.
“For now, the best course may be to reserve the early initiation of [ECMO] for those patients with infarct-related cardiogenic shock in whom the likely benefits more clearly outweigh the potential harms. We need further studies to tell us who they are,” write Dr. Leopold and Dr. Taichman, who are deputy editors with The New England Journal of Medicine.
ECLS-SHOCK randomly assigned 420 patients with acute MI complicated by shock and slated for coronary revascularization to receive standard care with or without early ECMO at 44 centers in Germany and Slovenia. Their median age was 63 years, and about 81% were men.
The relative risk for death from any cause, ECMO vs. usual care, was flatly nonsignificant at 0.98 (95% confidence interval, 0.80-1.19; P = .81).
ECMO came at the cost of significantly more cases of the primary safety endpoint, moderate or severe bleeding by Bleeding Academic Research Consortium criteria. That endpoint was met by 23.4% of ECMO patients and 9.6% of the control group, for an RR of 2.44 (95% CI, 1.50-3.95).
Rates of stroke or systemic embolization were nonsignificantly different at 3.8% and 2.9%, respectively (RR, 1.33; 95% CI, 0.47-3.76).
Speaking with this news organization, Sripal Bangalore, MD, MHA, pointed out that only 5.8% of the ECMO group but about 32% of those managed with usual care received some form of left ventricular (LV) unloading therapy.
Such measures can include atrial septostomy or the addition of an intra-aortic balloon pump or percutaneous LV-assist pump.
Given that ECMO increases afterload, “which is physiologically detrimental in patients with an ongoing MI, one is left to wonder if the results would have been different with greater use of LV unloading,” said Dr. Bangalore, of NYU Langone Health, New York, who isn’t associated with ECLS-SHOCK.
Also, he pointed out, about 78% of the trial’s patients had experienced some degree of cardiopulmonary resuscitation despite exclusion of anyone who had undergone it for more than 45 minutes. That may make the study more generalizable but also harder to show a benefit from ECMO. “The overall prognosis of that subset of patients despite heroic efforts is bleak at best.”
Dr. Thiele had no disclosures; statements for the other authors can be found at nejm.org. Dr. Bangalore has previously disclosed financial relationships with Abbott Vascular, Amgen, Biotronik, Inari, Pfizer, Reata, and Truvic. Dr. Leopold reports grants from Astellas and personal fees from United Therapeutics, Abbott Vascular, and North America Thrombosis Forum. Dr. Leopold and Dr. Taichman both report employment by The New England Journal of Medicine.
A version of this article appeared on Medscape.com.
Patients with acute myocardial infarction (MI) and shock are often put on extracorporeal membrane oxygenation (ECMO) support before heading to the catheterization laboratory. But the practice, done routinely, doesn’t have much backing from randomized trials. Now it’s being challenged by one of the largest such studies to explore the issue.
ECMO-managed patients, moreover, had sharply increased risks for moderate and severe bleeding and vascular complications.
A challenge to common practice
The results undercut guidelines that promote mechanical circulatory support in MI-related cardiogenic shock primarily based on observational data, and they argue against what’s become common practice, said Holger Thiele, MD, Heart Center Leipzig, University of Leipzig, Germany.
Such use of ECMO could well offer some type of advantage in MI-related shock, but the data so far don’t show it, Dr. Thiele said at a press conference on the new study, called ECLS-SHOCK, at the annual congress of the European Society of Cardiology in Amsterdam. He formally presented the trial at the meeting and is lead author on its simultaneous publication in The New England Journal of Medicine.
Almost half of the trial’s patients died, whether or not they had been put on ECMO. All-cause mortality at 30 days, the primary endpoint, was about the same, at 47.8% and 49.0% for the ECMO and usual-care groups, respectively.
Meanwhile, Dr. Thiele reported, risks for moderate or severe bleeding more than doubled and serious peripheral vascular complications almost tripled with addition of ECMO support.
The findings, he noted, are consistent with a new meta-analysis of trials testing ECMO in MI-related shock that also showed increases in bleeding with survival gains using the devices. Dr. Thiele is senior author on that report, published in The Lancet to coincide with his ECLS-SHOCK presentation.
Would any subgroups benefit?
Importantly, he said in an interview, ECMO’s failure to improve 30-day survival in the trial probably applies across the spectrum of patients with MI-related shock. Subgroup analyses in both ECLS-SHOCK and the meta-analysis didn’t identify any groups that benefit, Dr. Thiele observed.
For example, there were no significant differences for the primary outcome by age, sex, whether the MI was ST-segment elevation MI or non–ST-segment elevation MI or anterior or nonanterior, or whether the patient had diabetes.
If there is a subgroup in MI-related shock that is likely to benefit from the intervention with lower mortality, he said, “it’s less than 1%, if you ask me.”
An accompanying editorial essentially agreed, arguing that ECLS-SHOCK contests the intervention’s broad application in MI-related shock without shedding light on any selective benefits.
“Will the results of the ECLS-SHOCK trial change current clinical practice? If the goal of [ECMO] is to improve 30-day mortality, these data should steer interventional and critical care cardiologists away from its early routine implementation for all or even most patients with myocardial infarction and cardiogenic shock,” the editorialists say.
“There will be some patients in this population for whom [ECMO] is necessary and lifesaving, but the results of the ECLS-SHOCK trial do not tell us which ones,” write Jane A. Leopold, MD, Brigham and Women’s Hospital, Boston, and Darren B. Taichman, MD, PhD, Penn Presbyterian Medical Center, Philadelphia.
“For now, the best course may be to reserve the early initiation of [ECMO] for those patients with infarct-related cardiogenic shock in whom the likely benefits more clearly outweigh the potential harms. We need further studies to tell us who they are,” write Dr. Leopold and Dr. Taichman, who are deputy editors with The New England Journal of Medicine.
ECLS-SHOCK randomly assigned 420 patients with acute MI complicated by shock and slated for coronary revascularization to receive standard care with or without early ECMO at 44 centers in Germany and Slovenia. Their median age was 63 years, and about 81% were men.
The relative risk for death from any cause, ECMO vs. usual care, was flatly nonsignificant at 0.98 (95% confidence interval, 0.80-1.19; P = .81).
ECMO came at the cost of significantly more cases of the primary safety endpoint, moderate or severe bleeding by Bleeding Academic Research Consortium criteria. That endpoint was met by 23.4% of ECMO patients and 9.6% of the control group, for an RR of 2.44 (95% CI, 1.50-3.95).
Rates of stroke or systemic embolization were nonsignificantly different at 3.8% and 2.9%, respectively (RR, 1.33; 95% CI, 0.47-3.76).
Speaking with this news organization, Sripal Bangalore, MD, MHA, pointed out that only 5.8% of the ECMO group but about 32% of those managed with usual care received some form of left ventricular (LV) unloading therapy.
Such measures can include atrial septostomy or the addition of an intra-aortic balloon pump or percutaneous LV-assist pump.
Given that ECMO increases afterload, “which is physiologically detrimental in patients with an ongoing MI, one is left to wonder if the results would have been different with greater use of LV unloading,” said Dr. Bangalore, of NYU Langone Health, New York, who isn’t associated with ECLS-SHOCK.
Also, he pointed out, about 78% of the trial’s patients had experienced some degree of cardiopulmonary resuscitation despite exclusion of anyone who had undergone it for more than 45 minutes. That may make the study more generalizable but also harder to show a benefit from ECMO. “The overall prognosis of that subset of patients despite heroic efforts is bleak at best.”
Dr. Thiele had no disclosures; statements for the other authors can be found at nejm.org. Dr. Bangalore has previously disclosed financial relationships with Abbott Vascular, Amgen, Biotronik, Inari, Pfizer, Reata, and Truvic. Dr. Leopold reports grants from Astellas and personal fees from United Therapeutics, Abbott Vascular, and North America Thrombosis Forum. Dr. Leopold and Dr. Taichman both report employment by The New England Journal of Medicine.
A version of this article appeared on Medscape.com.
Patients with acute myocardial infarction (MI) and shock are often put on extracorporeal membrane oxygenation (ECMO) support before heading to the catheterization laboratory. But the practice, done routinely, doesn’t have much backing from randomized trials. Now it’s being challenged by one of the largest such studies to explore the issue.
ECMO-managed patients, moreover, had sharply increased risks for moderate and severe bleeding and vascular complications.
A challenge to common practice
The results undercut guidelines that promote mechanical circulatory support in MI-related cardiogenic shock primarily based on observational data, and they argue against what’s become common practice, said Holger Thiele, MD, Heart Center Leipzig, University of Leipzig, Germany.
Such use of ECMO could well offer some type of advantage in MI-related shock, but the data so far don’t show it, Dr. Thiele said at a press conference on the new study, called ECLS-SHOCK, at the annual congress of the European Society of Cardiology in Amsterdam. He formally presented the trial at the meeting and is lead author on its simultaneous publication in The New England Journal of Medicine.
Almost half of the trial’s patients died, whether or not they had been put on ECMO. All-cause mortality at 30 days, the primary endpoint, was about the same, at 47.8% and 49.0% for the ECMO and usual-care groups, respectively.
Meanwhile, Dr. Thiele reported, risks for moderate or severe bleeding more than doubled and serious peripheral vascular complications almost tripled with addition of ECMO support.
The findings, he noted, are consistent with a new meta-analysis of trials testing ECMO in MI-related shock that also showed increases in bleeding with survival gains using the devices. Dr. Thiele is senior author on that report, published in The Lancet to coincide with his ECLS-SHOCK presentation.
Would any subgroups benefit?
Importantly, he said in an interview, ECMO’s failure to improve 30-day survival in the trial probably applies across the spectrum of patients with MI-related shock. Subgroup analyses in both ECLS-SHOCK and the meta-analysis didn’t identify any groups that benefit, Dr. Thiele observed.
For example, there were no significant differences for the primary outcome by age, sex, whether the MI was ST-segment elevation MI or non–ST-segment elevation MI or anterior or nonanterior, or whether the patient had diabetes.
If there is a subgroup in MI-related shock that is likely to benefit from the intervention with lower mortality, he said, “it’s less than 1%, if you ask me.”
An accompanying editorial essentially agreed, arguing that ECLS-SHOCK contests the intervention’s broad application in MI-related shock without shedding light on any selective benefits.
“Will the results of the ECLS-SHOCK trial change current clinical practice? If the goal of [ECMO] is to improve 30-day mortality, these data should steer interventional and critical care cardiologists away from its early routine implementation for all or even most patients with myocardial infarction and cardiogenic shock,” the editorialists say.
“There will be some patients in this population for whom [ECMO] is necessary and lifesaving, but the results of the ECLS-SHOCK trial do not tell us which ones,” write Jane A. Leopold, MD, Brigham and Women’s Hospital, Boston, and Darren B. Taichman, MD, PhD, Penn Presbyterian Medical Center, Philadelphia.
“For now, the best course may be to reserve the early initiation of [ECMO] for those patients with infarct-related cardiogenic shock in whom the likely benefits more clearly outweigh the potential harms. We need further studies to tell us who they are,” write Dr. Leopold and Dr. Taichman, who are deputy editors with The New England Journal of Medicine.
ECLS-SHOCK randomly assigned 420 patients with acute MI complicated by shock and slated for coronary revascularization to receive standard care with or without early ECMO at 44 centers in Germany and Slovenia. Their median age was 63 years, and about 81% were men.
The relative risk for death from any cause, ECMO vs. usual care, was flatly nonsignificant at 0.98 (95% confidence interval, 0.80-1.19; P = .81).
ECMO came at the cost of significantly more cases of the primary safety endpoint, moderate or severe bleeding by Bleeding Academic Research Consortium criteria. That endpoint was met by 23.4% of ECMO patients and 9.6% of the control group, for an RR of 2.44 (95% CI, 1.50-3.95).
Rates of stroke or systemic embolization were nonsignificantly different at 3.8% and 2.9%, respectively (RR, 1.33; 95% CI, 0.47-3.76).
Speaking with this news organization, Sripal Bangalore, MD, MHA, pointed out that only 5.8% of the ECMO group but about 32% of those managed with usual care received some form of left ventricular (LV) unloading therapy.
Such measures can include atrial septostomy or the addition of an intra-aortic balloon pump or percutaneous LV-assist pump.
Given that ECMO increases afterload, “which is physiologically detrimental in patients with an ongoing MI, one is left to wonder if the results would have been different with greater use of LV unloading,” said Dr. Bangalore, of NYU Langone Health, New York, who isn’t associated with ECLS-SHOCK.
Also, he pointed out, about 78% of the trial’s patients had experienced some degree of cardiopulmonary resuscitation despite exclusion of anyone who had undergone it for more than 45 minutes. That may make the study more generalizable but also harder to show a benefit from ECMO. “The overall prognosis of that subset of patients despite heroic efforts is bleak at best.”
Dr. Thiele had no disclosures; statements for the other authors can be found at nejm.org. Dr. Bangalore has previously disclosed financial relationships with Abbott Vascular, Amgen, Biotronik, Inari, Pfizer, Reata, and Truvic. Dr. Leopold reports grants from Astellas and personal fees from United Therapeutics, Abbott Vascular, and North America Thrombosis Forum. Dr. Leopold and Dr. Taichman both report employment by The New England Journal of Medicine.
A version of this article appeared on Medscape.com.
FROM ESC CONGRESS 2023
Wegovy scores HFpEF benefits in people with obesity
AMSTERDAM – Adults with heart failure with preserved ejection fraction (HFpEF) but without diabetes showed significant improvements in their heart failure-related symptoms and physical limitations, exercise function, and weight loss when treated with a weight-reducing dose of semaglutide for 52 weeks, compared with placebo, in the randomized STEP-HFpEF trial.
The results, which also showed the treatment’s safety in these patients, “indicate that treatment with semaglutide is a valuable therapeutic approach in the management of patients with HFpEF and obesity,” Mikhail Kosiborod, MD, said at the annual congress of the European Society of Cardiology.
The findings establish semaglutide, a glucagonlike peptide–1 (GLP-1) receptor agonist, as a second class of medication with proven efficacy and safety for people with HFpEF, joining two agents also proven beneficial for people with HFpEF, dapagliflozin (Farxiga) and empagliflozin (Jardiance), both from the class of sodium-glucose cotransporter 2 (SGLT2) inhibitors.
When administered at the approved dose for weight loss of 2.4 mg, injected subcutaneously weekly for 52 weeks, semaglutide (Wegovy) produced an average 7.8-point incremental improvement in patients’ scores on the Kansas City Cardiomyopathy Questionnaire (KCCQ), a validated measure of symptoms and functional limitations, compared with controls who received placebo injections, as well as an average incremental weight loss from baseline, compared with placebo, of 10.7%. Both were significant effects, compared with placebo, and clinically meaningful benefits for the study’s two primary endpoints.
Simultaneously with Kosiborod’s report the results also appeared in a report posted online in the New England Journal of Medicine.
A ‘paradigm shift’ for medical weight loss in cardiology
The findings from this study with 529 randomized patients immediately propelled the weight loss formulation of semaglutide into the ranks of agents used to treat and prevent cardiovascular disease events. This evolution in the indications for semaglutide will be driven not only by the STEP-HFpEF results but also by findings from the SELECT trial, which tested the same semaglutide weight-loss dose in people with obesity, established cardiovascular disease, and had positive top-line results for prevention of major cardiovascular adverse events, according to a press release from Novo Nordisk on Aug. 8.
The STEP-HFpEF and SELECT results will trigger “a paradigm shift” for cardiologists, who will now need to consider prescribing a weight-loss medication to many of their patients, agents that until now were not part of the usual pharmacologic toolbox for cardiologists, said Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo. This shift will require education to bring the clinical cardiology community on board, he added in an interview.
Given that semaglutide administered at this dose already has a Food and Drug Administration–approved indication for weight loss in people with obesity or overweight plus at least one comorbidity, clinicians could immediately start using the treatment in people with obesity and HFpEF, said Dr. Kosiborod and other cardiologists.
Weekly semaglutide injections “could be considered a treatment option right now” for people with obesity and HFpEF, Dr. Kosiborod said during a press briefing.
Other experts agreed, especially because the STEP-HFpEF results confirmed that weight loss treatment with semaglutide was safe in this population.
‘A terrific win for patients’
The new findings are “a terrific win and game changer for patients with HFpEF,” commented Gregg C. Fonarow, MD, professor and cochief of cardiology at the University of California, Los Angeles, who was not involved with the study.
“The magnitude of improvement in the patient-reported health status scores are large and impressive. These data support clinical use of this agent for individuals with HFpEF with a body mass index of 30 kg/m2, patients who already fall within existing indications,” Dr. Fonarow said in an interview.
“Given the improvements in clinical outcomes in the STEP-HFpEF and SELECT trials, cardiologists should be prescribing these medications to eligible patients without conditions,” he added. “The perception of [semaglutide] needs to shift and be viewed as a component of the comprehensive medical therapies provided to individuals with established cardiovascular disease or HFpEF who also have elevated body mass index to improve their clinical outcomes.”
Historically, cardiologists have had a concern that weight loss was potentially harmful in people with heart failure and that obesity was protective, a phenomenon known as the “obesity paradox,” but the STEP-HFpEF data help disprove that notion, commented Nancy K. Sweitzer, MD, PhD, a heart failure specialist and vice chair of clinical research in the department of medicine at Washington University in St. Louis, who also was not involved in the study.
No signal of an obesity paradox
“There’s been a concern in the heart failure community to use weight-loss strategies in people with heart failure because of this, but this evidence provides a lot of confidence that it’s safe to use this weight loss treatment. The results show that patients feel better and lose weight with no signal of harm,” Dr. Sweitzer said in an interview.
The “encouraging findings” for semaglutide in patients with HFpEF “potentially add a much needed extra option for these patients and provide another upstream treatment for patients with signs of this condition plus a high body mass index,” commented Yigal M. Pinto, MD, PhD, in an editorial that accompanied the published report.
“How these findings translate to hard end points remains to be established and will be important in determining the role of GLP-1 agonism,” wrote Dr. Pinto, a professor and heart failure specialist at Amsterdam University Medical Center.
But Dr. Kosiborod said that the improvement seen in the KCCQ score was itself an important benefit for patients. “Heart failure is defined clinically based on symptoms,” he noted, and results in prior studies documented that patients value improvements in symptoms and physical limitations even more than they value “hard endpoints” such as survival.
The new findings, which indicate that two different and expensive classes of medications are now standard of care for many people with HFpEF and obesity – the SGLT2 inhibitors and the GLP-1 receptor agonist semaglutide – also raise concerns over patient access and affordability, as many U.S. insurers have a history of requiring prior authorization, high copays, or coverage denials for these two medical classes.
But Dr. Sweitzer and Dr. Kosiborod both said that the insurance-coverage climate seems, in just the past couple of years or so, to have dramatically improved, although it’s still not ideal.
Prior authorization hoops have decreased
“We still have prior-authorization hoops to jump through, but I expect these will continue to decrease over time as evidence for clinical benefits [from weight loss] continues to accumulate,” said Dr. Sweitzer.
And “the SELECT data mean that cardiologists will need to become comfortable prescribing GLP-1 receptor agonists,” she added.
“It’s not okay for insurers to say we are not going to cover weight loss medications because it’s a cosmetic indication,” said Dr. Kosiborod. “Obesity appears to be very important in the pathogenesis and progression of heart failure, and if patients derive substantial benefit, they should have access to this treatment.”
The improvements in KCCQ score, as well as in several secondary and exploratory endpoints including a significant reduction in C-reactive protein (an indication of a potent anti-inflammatory effect), an average 20 m increase in 6-minute walk distance, a significant average drop in N-terminal pro-brain natriuretic peptide, and a drop in heart failure hospitalizations or urgent heart failure visits (although the trial was not powered to show differences in clinical events), “were the largest benefits in these outcomes we’ve seen,” compared with any other medical intervention in people with HFpEF, he noted.
“About 80% of U.S. patients with HFpEF have obesity or overweight,” Dr. Kosiborod noted. Using semaglutide on these patients “is an issue of access and insurance coverage. My hope is that these and other data will favorably change this.”
A related trial with a similar design, STEP-HFpEF DM, is still in progress and testing the same semaglutide treatment in adults with HFpEF, obesity, and type 2 diabetes, noted Dr. Kosiborod, who is also lead investigator for that study. He said those results will likely become available before the end of 2023.
The study was funded by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Kosiborod has been a consultant and adviser to and has received honoraria from Novo Nordisk. He has also been a consultant to numerous other companies, received research grants from AstraZeneca, Boehringer Ingelheim, and Pfizer, honoraria from AstraZeneca, and is a stockholder in Artera Health and Saghmos Therapeutics. Dr. Fonarow has been a consultant to Abbott, Amgen, AstraZeneca, CHF Solutions, Cytokinetics, Edwards, Janssen, Medtronic, Merck, Novartis, and Regeneron. Dr. Sweitzer reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AMSTERDAM – Adults with heart failure with preserved ejection fraction (HFpEF) but without diabetes showed significant improvements in their heart failure-related symptoms and physical limitations, exercise function, and weight loss when treated with a weight-reducing dose of semaglutide for 52 weeks, compared with placebo, in the randomized STEP-HFpEF trial.
The results, which also showed the treatment’s safety in these patients, “indicate that treatment with semaglutide is a valuable therapeutic approach in the management of patients with HFpEF and obesity,” Mikhail Kosiborod, MD, said at the annual congress of the European Society of Cardiology.
The findings establish semaglutide, a glucagonlike peptide–1 (GLP-1) receptor agonist, as a second class of medication with proven efficacy and safety for people with HFpEF, joining two agents also proven beneficial for people with HFpEF, dapagliflozin (Farxiga) and empagliflozin (Jardiance), both from the class of sodium-glucose cotransporter 2 (SGLT2) inhibitors.
When administered at the approved dose for weight loss of 2.4 mg, injected subcutaneously weekly for 52 weeks, semaglutide (Wegovy) produced an average 7.8-point incremental improvement in patients’ scores on the Kansas City Cardiomyopathy Questionnaire (KCCQ), a validated measure of symptoms and functional limitations, compared with controls who received placebo injections, as well as an average incremental weight loss from baseline, compared with placebo, of 10.7%. Both were significant effects, compared with placebo, and clinically meaningful benefits for the study’s two primary endpoints.
Simultaneously with Kosiborod’s report the results also appeared in a report posted online in the New England Journal of Medicine.
A ‘paradigm shift’ for medical weight loss in cardiology
The findings from this study with 529 randomized patients immediately propelled the weight loss formulation of semaglutide into the ranks of agents used to treat and prevent cardiovascular disease events. This evolution in the indications for semaglutide will be driven not only by the STEP-HFpEF results but also by findings from the SELECT trial, which tested the same semaglutide weight-loss dose in people with obesity, established cardiovascular disease, and had positive top-line results for prevention of major cardiovascular adverse events, according to a press release from Novo Nordisk on Aug. 8.
The STEP-HFpEF and SELECT results will trigger “a paradigm shift” for cardiologists, who will now need to consider prescribing a weight-loss medication to many of their patients, agents that until now were not part of the usual pharmacologic toolbox for cardiologists, said Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo. This shift will require education to bring the clinical cardiology community on board, he added in an interview.
Given that semaglutide administered at this dose already has a Food and Drug Administration–approved indication for weight loss in people with obesity or overweight plus at least one comorbidity, clinicians could immediately start using the treatment in people with obesity and HFpEF, said Dr. Kosiborod and other cardiologists.
Weekly semaglutide injections “could be considered a treatment option right now” for people with obesity and HFpEF, Dr. Kosiborod said during a press briefing.
Other experts agreed, especially because the STEP-HFpEF results confirmed that weight loss treatment with semaglutide was safe in this population.
‘A terrific win for patients’
The new findings are “a terrific win and game changer for patients with HFpEF,” commented Gregg C. Fonarow, MD, professor and cochief of cardiology at the University of California, Los Angeles, who was not involved with the study.
“The magnitude of improvement in the patient-reported health status scores are large and impressive. These data support clinical use of this agent for individuals with HFpEF with a body mass index of 30 kg/m2, patients who already fall within existing indications,” Dr. Fonarow said in an interview.
“Given the improvements in clinical outcomes in the STEP-HFpEF and SELECT trials, cardiologists should be prescribing these medications to eligible patients without conditions,” he added. “The perception of [semaglutide] needs to shift and be viewed as a component of the comprehensive medical therapies provided to individuals with established cardiovascular disease or HFpEF who also have elevated body mass index to improve their clinical outcomes.”
Historically, cardiologists have had a concern that weight loss was potentially harmful in people with heart failure and that obesity was protective, a phenomenon known as the “obesity paradox,” but the STEP-HFpEF data help disprove that notion, commented Nancy K. Sweitzer, MD, PhD, a heart failure specialist and vice chair of clinical research in the department of medicine at Washington University in St. Louis, who also was not involved in the study.
No signal of an obesity paradox
“There’s been a concern in the heart failure community to use weight-loss strategies in people with heart failure because of this, but this evidence provides a lot of confidence that it’s safe to use this weight loss treatment. The results show that patients feel better and lose weight with no signal of harm,” Dr. Sweitzer said in an interview.
The “encouraging findings” for semaglutide in patients with HFpEF “potentially add a much needed extra option for these patients and provide another upstream treatment for patients with signs of this condition plus a high body mass index,” commented Yigal M. Pinto, MD, PhD, in an editorial that accompanied the published report.
“How these findings translate to hard end points remains to be established and will be important in determining the role of GLP-1 agonism,” wrote Dr. Pinto, a professor and heart failure specialist at Amsterdam University Medical Center.
But Dr. Kosiborod said that the improvement seen in the KCCQ score was itself an important benefit for patients. “Heart failure is defined clinically based on symptoms,” he noted, and results in prior studies documented that patients value improvements in symptoms and physical limitations even more than they value “hard endpoints” such as survival.
The new findings, which indicate that two different and expensive classes of medications are now standard of care for many people with HFpEF and obesity – the SGLT2 inhibitors and the GLP-1 receptor agonist semaglutide – also raise concerns over patient access and affordability, as many U.S. insurers have a history of requiring prior authorization, high copays, or coverage denials for these two medical classes.
But Dr. Sweitzer and Dr. Kosiborod both said that the insurance-coverage climate seems, in just the past couple of years or so, to have dramatically improved, although it’s still not ideal.
Prior authorization hoops have decreased
“We still have prior-authorization hoops to jump through, but I expect these will continue to decrease over time as evidence for clinical benefits [from weight loss] continues to accumulate,” said Dr. Sweitzer.
And “the SELECT data mean that cardiologists will need to become comfortable prescribing GLP-1 receptor agonists,” she added.
“It’s not okay for insurers to say we are not going to cover weight loss medications because it’s a cosmetic indication,” said Dr. Kosiborod. “Obesity appears to be very important in the pathogenesis and progression of heart failure, and if patients derive substantial benefit, they should have access to this treatment.”
The improvements in KCCQ score, as well as in several secondary and exploratory endpoints including a significant reduction in C-reactive protein (an indication of a potent anti-inflammatory effect), an average 20 m increase in 6-minute walk distance, a significant average drop in N-terminal pro-brain natriuretic peptide, and a drop in heart failure hospitalizations or urgent heart failure visits (although the trial was not powered to show differences in clinical events), “were the largest benefits in these outcomes we’ve seen,” compared with any other medical intervention in people with HFpEF, he noted.
“About 80% of U.S. patients with HFpEF have obesity or overweight,” Dr. Kosiborod noted. Using semaglutide on these patients “is an issue of access and insurance coverage. My hope is that these and other data will favorably change this.”
A related trial with a similar design, STEP-HFpEF DM, is still in progress and testing the same semaglutide treatment in adults with HFpEF, obesity, and type 2 diabetes, noted Dr. Kosiborod, who is also lead investigator for that study. He said those results will likely become available before the end of 2023.
The study was funded by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Kosiborod has been a consultant and adviser to and has received honoraria from Novo Nordisk. He has also been a consultant to numerous other companies, received research grants from AstraZeneca, Boehringer Ingelheim, and Pfizer, honoraria from AstraZeneca, and is a stockholder in Artera Health and Saghmos Therapeutics. Dr. Fonarow has been a consultant to Abbott, Amgen, AstraZeneca, CHF Solutions, Cytokinetics, Edwards, Janssen, Medtronic, Merck, Novartis, and Regeneron. Dr. Sweitzer reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AMSTERDAM – Adults with heart failure with preserved ejection fraction (HFpEF) but without diabetes showed significant improvements in their heart failure-related symptoms and physical limitations, exercise function, and weight loss when treated with a weight-reducing dose of semaglutide for 52 weeks, compared with placebo, in the randomized STEP-HFpEF trial.
The results, which also showed the treatment’s safety in these patients, “indicate that treatment with semaglutide is a valuable therapeutic approach in the management of patients with HFpEF and obesity,” Mikhail Kosiborod, MD, said at the annual congress of the European Society of Cardiology.
The findings establish semaglutide, a glucagonlike peptide–1 (GLP-1) receptor agonist, as a second class of medication with proven efficacy and safety for people with HFpEF, joining two agents also proven beneficial for people with HFpEF, dapagliflozin (Farxiga) and empagliflozin (Jardiance), both from the class of sodium-glucose cotransporter 2 (SGLT2) inhibitors.
When administered at the approved dose for weight loss of 2.4 mg, injected subcutaneously weekly for 52 weeks, semaglutide (Wegovy) produced an average 7.8-point incremental improvement in patients’ scores on the Kansas City Cardiomyopathy Questionnaire (KCCQ), a validated measure of symptoms and functional limitations, compared with controls who received placebo injections, as well as an average incremental weight loss from baseline, compared with placebo, of 10.7%. Both were significant effects, compared with placebo, and clinically meaningful benefits for the study’s two primary endpoints.
Simultaneously with Kosiborod’s report the results also appeared in a report posted online in the New England Journal of Medicine.
A ‘paradigm shift’ for medical weight loss in cardiology
The findings from this study with 529 randomized patients immediately propelled the weight loss formulation of semaglutide into the ranks of agents used to treat and prevent cardiovascular disease events. This evolution in the indications for semaglutide will be driven not only by the STEP-HFpEF results but also by findings from the SELECT trial, which tested the same semaglutide weight-loss dose in people with obesity, established cardiovascular disease, and had positive top-line results for prevention of major cardiovascular adverse events, according to a press release from Novo Nordisk on Aug. 8.
The STEP-HFpEF and SELECT results will trigger “a paradigm shift” for cardiologists, who will now need to consider prescribing a weight-loss medication to many of their patients, agents that until now were not part of the usual pharmacologic toolbox for cardiologists, said Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo. This shift will require education to bring the clinical cardiology community on board, he added in an interview.
Given that semaglutide administered at this dose already has a Food and Drug Administration–approved indication for weight loss in people with obesity or overweight plus at least one comorbidity, clinicians could immediately start using the treatment in people with obesity and HFpEF, said Dr. Kosiborod and other cardiologists.
Weekly semaglutide injections “could be considered a treatment option right now” for people with obesity and HFpEF, Dr. Kosiborod said during a press briefing.
Other experts agreed, especially because the STEP-HFpEF results confirmed that weight loss treatment with semaglutide was safe in this population.
‘A terrific win for patients’
The new findings are “a terrific win and game changer for patients with HFpEF,” commented Gregg C. Fonarow, MD, professor and cochief of cardiology at the University of California, Los Angeles, who was not involved with the study.
“The magnitude of improvement in the patient-reported health status scores are large and impressive. These data support clinical use of this agent for individuals with HFpEF with a body mass index of 30 kg/m2, patients who already fall within existing indications,” Dr. Fonarow said in an interview.
“Given the improvements in clinical outcomes in the STEP-HFpEF and SELECT trials, cardiologists should be prescribing these medications to eligible patients without conditions,” he added. “The perception of [semaglutide] needs to shift and be viewed as a component of the comprehensive medical therapies provided to individuals with established cardiovascular disease or HFpEF who also have elevated body mass index to improve their clinical outcomes.”
Historically, cardiologists have had a concern that weight loss was potentially harmful in people with heart failure and that obesity was protective, a phenomenon known as the “obesity paradox,” but the STEP-HFpEF data help disprove that notion, commented Nancy K. Sweitzer, MD, PhD, a heart failure specialist and vice chair of clinical research in the department of medicine at Washington University in St. Louis, who also was not involved in the study.
No signal of an obesity paradox
“There’s been a concern in the heart failure community to use weight-loss strategies in people with heart failure because of this, but this evidence provides a lot of confidence that it’s safe to use this weight loss treatment. The results show that patients feel better and lose weight with no signal of harm,” Dr. Sweitzer said in an interview.
The “encouraging findings” for semaglutide in patients with HFpEF “potentially add a much needed extra option for these patients and provide another upstream treatment for patients with signs of this condition plus a high body mass index,” commented Yigal M. Pinto, MD, PhD, in an editorial that accompanied the published report.
“How these findings translate to hard end points remains to be established and will be important in determining the role of GLP-1 agonism,” wrote Dr. Pinto, a professor and heart failure specialist at Amsterdam University Medical Center.
But Dr. Kosiborod said that the improvement seen in the KCCQ score was itself an important benefit for patients. “Heart failure is defined clinically based on symptoms,” he noted, and results in prior studies documented that patients value improvements in symptoms and physical limitations even more than they value “hard endpoints” such as survival.
The new findings, which indicate that two different and expensive classes of medications are now standard of care for many people with HFpEF and obesity – the SGLT2 inhibitors and the GLP-1 receptor agonist semaglutide – also raise concerns over patient access and affordability, as many U.S. insurers have a history of requiring prior authorization, high copays, or coverage denials for these two medical classes.
But Dr. Sweitzer and Dr. Kosiborod both said that the insurance-coverage climate seems, in just the past couple of years or so, to have dramatically improved, although it’s still not ideal.
Prior authorization hoops have decreased
“We still have prior-authorization hoops to jump through, but I expect these will continue to decrease over time as evidence for clinical benefits [from weight loss] continues to accumulate,” said Dr. Sweitzer.
And “the SELECT data mean that cardiologists will need to become comfortable prescribing GLP-1 receptor agonists,” she added.
“It’s not okay for insurers to say we are not going to cover weight loss medications because it’s a cosmetic indication,” said Dr. Kosiborod. “Obesity appears to be very important in the pathogenesis and progression of heart failure, and if patients derive substantial benefit, they should have access to this treatment.”
The improvements in KCCQ score, as well as in several secondary and exploratory endpoints including a significant reduction in C-reactive protein (an indication of a potent anti-inflammatory effect), an average 20 m increase in 6-minute walk distance, a significant average drop in N-terminal pro-brain natriuretic peptide, and a drop in heart failure hospitalizations or urgent heart failure visits (although the trial was not powered to show differences in clinical events), “were the largest benefits in these outcomes we’ve seen,” compared with any other medical intervention in people with HFpEF, he noted.
“About 80% of U.S. patients with HFpEF have obesity or overweight,” Dr. Kosiborod noted. Using semaglutide on these patients “is an issue of access and insurance coverage. My hope is that these and other data will favorably change this.”
A related trial with a similar design, STEP-HFpEF DM, is still in progress and testing the same semaglutide treatment in adults with HFpEF, obesity, and type 2 diabetes, noted Dr. Kosiborod, who is also lead investigator for that study. He said those results will likely become available before the end of 2023.
The study was funded by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Kosiborod has been a consultant and adviser to and has received honoraria from Novo Nordisk. He has also been a consultant to numerous other companies, received research grants from AstraZeneca, Boehringer Ingelheim, and Pfizer, honoraria from AstraZeneca, and is a stockholder in Artera Health and Saghmos Therapeutics. Dr. Fonarow has been a consultant to Abbott, Amgen, AstraZeneca, CHF Solutions, Cytokinetics, Edwards, Janssen, Medtronic, Merck, Novartis, and Regeneron. Dr. Sweitzer reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT THE ESC CONGRESS 2023
Dementia diagnosis a good time to reduce polypharmacy
Physicians may be missing opportunities to reduce harmful polypharmacy in elderly patients with newly diagnosed dementia, investigators for a large study of Medicare beneficiaries reported.
They found that those with an incident dementia diagnosis were somewhat more likely to initiate central nervous system–active medications and slightly more likely to discontinue cardiometabolic and anticholinergic medications, compared with controls.
According to the authors, time of diagnosis can be a potential inflexion point for deprescribing long-term medications with high safety risks, limited likelihood of benefit, or possible association with impaired cognition.
“Understanding the chronology of medication changes following a first dementia diagnosis may identify targets for deprescribing interventions to reduce preventable medication-related harms, said Timothy S. Anderson, MD, MAS, of the division of general medicine at Beth Israel Deaconess Medical Center, Boston, and colleagues in JAMA Internal Medicine.
“Our results provide a baseline to inform efforts to rethink the clinical approach to medication use at the time of a new dementia diagnosis.”
Hundreds of thousands of Americans are diagnosed annually with Alzheimer’s and related dementias, the authors pointed out, and the majority have multiple other chronic conditions. Worsening cognitive impairment may alter the risk-benefit balance of medications taken for these conditions.
Matched cohort study
The sample consisted of adults 67 years or older enrolled in traditional Medicare and Medicare Part D. Patients with an initial incident dementia diagnosis between January 2012 and December 2018 were matched with controls (as of last doctor’s office visit) based on demographics, geographic location, and baseline medication count. Data were analyzed from 2021 to June 2023.
The study included 266,675 adults with incident dementia and 266,675 controls. In both groups, 65.1% were 80 years or older (mean age, 82.2) and 67.8% were female. At baseline, patients with incident dementia were more likely than controls to use CNS-active medications (54.32% vs. 48.39%) and anticholinergic medications (17.79% vs. 15.96%) and less likely to use most cardiometabolic medications (for example, antidiabetics, 31.19% vs. 36.45%).
Immediately following the index diagnosis, the dementia cohort had greater increases in the mean number of medications used: 0.41 vs. –0.06 (95% confidence interval, 0.27-0.66) and in the proportion using CNS-active medications (absolute change, 3.44% vs. 0.79%; 95% CI, 0.85%-4.45%). The rise was because of an increased use of antipsychotics, antidepressants, and antiepileptics.
The affected cohort showed a modestly greater decline in anticholinergic medications: quarterly change in use: −0.53% vs. −0.21% (95% CI, −0.55% to −0.08%); and in most cardiometabolic medications: for example, quarterly change in antihypertensive use: –0.84% vs. –0.40% (95% CI, –0.64% to –0.25%). Still, a year post diagnosis, 75.2% of dementia patients were using five or more medications, for a 2.8% increase.
The drug classes with the steepest rate of discontinuation – such as lipid-lowering and antihypertensive medications – had low risks for adverse drug events, while higher-risk classes – such as insulins and antiplatelet and anticoagulant agents – had smaller or no reductions in use.
While the findings point to opportunities to reduce polypharmacy by deprescribing long-term medications of dubious benefit, interventions to reduce polypharmacy and inappropriate medications have been modestly successful for patients without dementia, the authors said. But the recent OPTIMIZE trial, an educational effort aimed at primary care clinicians and patients with cognitive impairment, reduced neither polypharmacy nor potentially inappropriate medications.
Luke D. Kim, MD, a geriatrician at the Cleveland Clinic in Ohio, agreed that seniors with dementia can benefit from reassessment of their pharmacologic therapies. “Older adults in general are more prone to have side effects from medications as their renal and hepatic clearance and metabolism are different and lower than those of younger individuals. But they tend to take multiple medications owing to more comorbidities,” said Dr. Kim, who was not involved in the study. “While all older adults need to be more careful about medication management, those with dementia need an even more careful approach as they have diminished cognitive reserve and risk more potential harm from medications.”
The authors noted that since decision-making models aligned with patient priorities for older adults without dementia led to reductions in overall medication use, that may be a path forward in populations with dementia.
The study was supported by grants from the National Institute on Aging, National Institutes of Health. The authors had no competing interests to disclose. Dr. Kim disclosed no competing interests relevant to his comments.
Physicians may be missing opportunities to reduce harmful polypharmacy in elderly patients with newly diagnosed dementia, investigators for a large study of Medicare beneficiaries reported.
They found that those with an incident dementia diagnosis were somewhat more likely to initiate central nervous system–active medications and slightly more likely to discontinue cardiometabolic and anticholinergic medications, compared with controls.
According to the authors, time of diagnosis can be a potential inflexion point for deprescribing long-term medications with high safety risks, limited likelihood of benefit, or possible association with impaired cognition.
“Understanding the chronology of medication changes following a first dementia diagnosis may identify targets for deprescribing interventions to reduce preventable medication-related harms, said Timothy S. Anderson, MD, MAS, of the division of general medicine at Beth Israel Deaconess Medical Center, Boston, and colleagues in JAMA Internal Medicine.
“Our results provide a baseline to inform efforts to rethink the clinical approach to medication use at the time of a new dementia diagnosis.”
Hundreds of thousands of Americans are diagnosed annually with Alzheimer’s and related dementias, the authors pointed out, and the majority have multiple other chronic conditions. Worsening cognitive impairment may alter the risk-benefit balance of medications taken for these conditions.
Matched cohort study
The sample consisted of adults 67 years or older enrolled in traditional Medicare and Medicare Part D. Patients with an initial incident dementia diagnosis between January 2012 and December 2018 were matched with controls (as of last doctor’s office visit) based on demographics, geographic location, and baseline medication count. Data were analyzed from 2021 to June 2023.
The study included 266,675 adults with incident dementia and 266,675 controls. In both groups, 65.1% were 80 years or older (mean age, 82.2) and 67.8% were female. At baseline, patients with incident dementia were more likely than controls to use CNS-active medications (54.32% vs. 48.39%) and anticholinergic medications (17.79% vs. 15.96%) and less likely to use most cardiometabolic medications (for example, antidiabetics, 31.19% vs. 36.45%).
Immediately following the index diagnosis, the dementia cohort had greater increases in the mean number of medications used: 0.41 vs. –0.06 (95% confidence interval, 0.27-0.66) and in the proportion using CNS-active medications (absolute change, 3.44% vs. 0.79%; 95% CI, 0.85%-4.45%). The rise was because of an increased use of antipsychotics, antidepressants, and antiepileptics.
The affected cohort showed a modestly greater decline in anticholinergic medications: quarterly change in use: −0.53% vs. −0.21% (95% CI, −0.55% to −0.08%); and in most cardiometabolic medications: for example, quarterly change in antihypertensive use: –0.84% vs. –0.40% (95% CI, –0.64% to –0.25%). Still, a year post diagnosis, 75.2% of dementia patients were using five or more medications, for a 2.8% increase.
The drug classes with the steepest rate of discontinuation – such as lipid-lowering and antihypertensive medications – had low risks for adverse drug events, while higher-risk classes – such as insulins and antiplatelet and anticoagulant agents – had smaller or no reductions in use.
While the findings point to opportunities to reduce polypharmacy by deprescribing long-term medications of dubious benefit, interventions to reduce polypharmacy and inappropriate medications have been modestly successful for patients without dementia, the authors said. But the recent OPTIMIZE trial, an educational effort aimed at primary care clinicians and patients with cognitive impairment, reduced neither polypharmacy nor potentially inappropriate medications.
Luke D. Kim, MD, a geriatrician at the Cleveland Clinic in Ohio, agreed that seniors with dementia can benefit from reassessment of their pharmacologic therapies. “Older adults in general are more prone to have side effects from medications as their renal and hepatic clearance and metabolism are different and lower than those of younger individuals. But they tend to take multiple medications owing to more comorbidities,” said Dr. Kim, who was not involved in the study. “While all older adults need to be more careful about medication management, those with dementia need an even more careful approach as they have diminished cognitive reserve and risk more potential harm from medications.”
The authors noted that since decision-making models aligned with patient priorities for older adults without dementia led to reductions in overall medication use, that may be a path forward in populations with dementia.
The study was supported by grants from the National Institute on Aging, National Institutes of Health. The authors had no competing interests to disclose. Dr. Kim disclosed no competing interests relevant to his comments.
Physicians may be missing opportunities to reduce harmful polypharmacy in elderly patients with newly diagnosed dementia, investigators for a large study of Medicare beneficiaries reported.
They found that those with an incident dementia diagnosis were somewhat more likely to initiate central nervous system–active medications and slightly more likely to discontinue cardiometabolic and anticholinergic medications, compared with controls.
According to the authors, time of diagnosis can be a potential inflexion point for deprescribing long-term medications with high safety risks, limited likelihood of benefit, or possible association with impaired cognition.
“Understanding the chronology of medication changes following a first dementia diagnosis may identify targets for deprescribing interventions to reduce preventable medication-related harms, said Timothy S. Anderson, MD, MAS, of the division of general medicine at Beth Israel Deaconess Medical Center, Boston, and colleagues in JAMA Internal Medicine.
“Our results provide a baseline to inform efforts to rethink the clinical approach to medication use at the time of a new dementia diagnosis.”
Hundreds of thousands of Americans are diagnosed annually with Alzheimer’s and related dementias, the authors pointed out, and the majority have multiple other chronic conditions. Worsening cognitive impairment may alter the risk-benefit balance of medications taken for these conditions.
Matched cohort study
The sample consisted of adults 67 years or older enrolled in traditional Medicare and Medicare Part D. Patients with an initial incident dementia diagnosis between January 2012 and December 2018 were matched with controls (as of last doctor’s office visit) based on demographics, geographic location, and baseline medication count. Data were analyzed from 2021 to June 2023.
The study included 266,675 adults with incident dementia and 266,675 controls. In both groups, 65.1% were 80 years or older (mean age, 82.2) and 67.8% were female. At baseline, patients with incident dementia were more likely than controls to use CNS-active medications (54.32% vs. 48.39%) and anticholinergic medications (17.79% vs. 15.96%) and less likely to use most cardiometabolic medications (for example, antidiabetics, 31.19% vs. 36.45%).
Immediately following the index diagnosis, the dementia cohort had greater increases in the mean number of medications used: 0.41 vs. –0.06 (95% confidence interval, 0.27-0.66) and in the proportion using CNS-active medications (absolute change, 3.44% vs. 0.79%; 95% CI, 0.85%-4.45%). The rise was because of an increased use of antipsychotics, antidepressants, and antiepileptics.
The affected cohort showed a modestly greater decline in anticholinergic medications: quarterly change in use: −0.53% vs. −0.21% (95% CI, −0.55% to −0.08%); and in most cardiometabolic medications: for example, quarterly change in antihypertensive use: –0.84% vs. –0.40% (95% CI, –0.64% to –0.25%). Still, a year post diagnosis, 75.2% of dementia patients were using five or more medications, for a 2.8% increase.
The drug classes with the steepest rate of discontinuation – such as lipid-lowering and antihypertensive medications – had low risks for adverse drug events, while higher-risk classes – such as insulins and antiplatelet and anticoagulant agents – had smaller or no reductions in use.
While the findings point to opportunities to reduce polypharmacy by deprescribing long-term medications of dubious benefit, interventions to reduce polypharmacy and inappropriate medications have been modestly successful for patients without dementia, the authors said. But the recent OPTIMIZE trial, an educational effort aimed at primary care clinicians and patients with cognitive impairment, reduced neither polypharmacy nor potentially inappropriate medications.
Luke D. Kim, MD, a geriatrician at the Cleveland Clinic in Ohio, agreed that seniors with dementia can benefit from reassessment of their pharmacologic therapies. “Older adults in general are more prone to have side effects from medications as their renal and hepatic clearance and metabolism are different and lower than those of younger individuals. But they tend to take multiple medications owing to more comorbidities,” said Dr. Kim, who was not involved in the study. “While all older adults need to be more careful about medication management, those with dementia need an even more careful approach as they have diminished cognitive reserve and risk more potential harm from medications.”
The authors noted that since decision-making models aligned with patient priorities for older adults without dementia led to reductions in overall medication use, that may be a path forward in populations with dementia.
The study was supported by grants from the National Institute on Aging, National Institutes of Health. The authors had no competing interests to disclose. Dr. Kim disclosed no competing interests relevant to his comments.
FROM JAMA INTERNAL MEDICINE
Simple blood test may predict heart and kidney risk in T2D
, suggests an analysis of the CREDENCE trial.
The research, published online in the journal Circulation, also revealed that patients treated with the sodium-glucose cotransporter-2 inhibitor canagliflozin (Invokana, Invokamet) had lower levels of the biomarkers after 1 year compared with those given placebo.
Examination of biomarker levels in more than 2,600 patients from CREDENCE showed that high baseline concentrations of the individual biomarkers were able to predict the future risk for a composite endpoint of renal and heart outcomes.
The combination of all four biomarkers into a single panel revealed that patients with the highest levels were more than four times as likely to experience the composite endpoint than were those with the lowest levels.
As two of the biomarkers used in the study have yet to have established prognostic thresholds, the results remain exploratory.
Lead author James L. Januzzi, MD, director of the Heart Failure and Biomarker Trials at the Baim Institute for Clinical Research, Boston, said that further study will help refine the predictive value of the panel.
“Given that the American Heart Association/American College of Cardiology and the American Diabetes Association now all recommend measurement of biomarkers to enhance the ability to predict risk in persons with type 2 diabetes, these results may considerably extend the reach of biomarker-based testing, refining accuracy even further,” he said in a press release.
In an interview, Dr. Januzzi said that “three out of the four biomarkers are already clinically and commercially available,” while the fourth, for insulin-like growth factor binding protein 7 (IGFBP7), is “on the near horizon.”
He stressed that the “future for multiple biomarker testing, however, will be less about ordering each individual test, and ultimately will revolve around panels of blood work that are ordered as a single test.”
Dr. Januzzi added that “rather than using the rather primitive approach that we took” of looking at the individual biomarkers in adjusted models, the next stage “will be to utilize algorithms to combine the results into a single value.
“A clinician will not have to struggle with looking at individual results but will just receive one aggregated test result that informs them whether a patient is at low, medium or higher risk,” he explained.
However, this will require determining the relative importance of each biomarker and weighting them in the final model.
Consequently, the current results “set the foundation for identifying some very powerful individual tests that may ultimately, in aggregate, help us to help our patients with diabetes avoid a major complication,” Dr. Januzzi said.
By revealing that some individuals with both type 2 diabetes and kidney disease are at higher risk than others, he also hopes the findings can be leveraged to treat patients with “varying degrees of intensity with proven therapies, including weight loss, dietary adjustment, and pharmacologic intervention.”
Dr. Januzzi added: “Diabetes affects a dramatic, and growing, percentage of our population, and this type of personalized strategy to reduce the major complications of this rather common disease is an important step forward.”
The authors noted that there is a “bidirectional relationship” between cardiovascular disease and chronic kidney disease (CKD), such that either diagnosis may increase the risk of, or exacerbate, the other.
Individuals with type 2 diabetes and CKD albuminuria, they added, are at particularly high risk for major cardiovascular events, and studies have shown that several circulating cardiorenal stress biomarkers may predict the onset and progression of CKD in type 2 diabetes, as well as predict cardiovascular events.
Several biomarkers associated with myocardial stress and necrosis
The recent CANVAS trial revealed that, among individuals with type 2 diabetes with and without CKD, several biomarkers were associated with myocardial stress and necrosis, and renal tubular injury, predicting the progression of CKD with albuminuria, and the risk for heart failure events.
Taking inspiration from those findings, the current researchers studied a panel of similar cardiac and renal biomarkers among participants from the CREDENCE trial, for which 4,401 patients with type 2 diabetes and CKD at high risk of progression were randomly assigned to canagliflozin or placebo.
The current analysis involved 2,627 participants who had baseline plasma samples available for analysis of four circulating biomarkers: N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), growth differentiation factor-15 (GDF-15), and IGFBP7.
Among those, 2,385 participants also had year 1 plasma samples available for analysis, while year 3 plasma samples were available for 895 individuals.
The results showed that, in general, median baseline concentrations of each biomarker in both treatment groups were elevated compared with healthy reference populations.
Baseline log-transformed concentrations of each biomarker were also strongly predictive of cardiac and renal outcomes, including heart failure and progression of CKD.
For example, each unit increase in baseline NT-proBNP concentrations was associated with a hazard ratio of 1.35 for the primary composite endpoint of end-stage kidney disease, doubling of serum creatinine levels, renal death, or cardiovascular disease (P < .001).
For each unit increase in hs-cTnT levels, the hazard ratio for the primary composite was 1.73 (P < .001), for GDF-15 it was 1.84 (P < .0001), and for IGFBP7 the hazard ratio was 3.14 (P < .001).
Combining the four biomarkers into a single multimarker panel revealed that, compared with individuals with a low-risk score, those with a high-risk score had a hazard ratio for the primary outcome of 4.01, whereas those with a moderate risk score had a hazard ratio of 2.39 (P < .001 for both).
For the individual outcome of heart failure hospitalization, the effect was even greater. A high-risk score was associated with a hazard ratio vs. a low-risk score of 6.04 (P < .001), whereas patients with a moderate risk score had a hazard ratio of 2.45 (P = .04).
The researchers also reported that, between baseline and year 1, concentrations of all four biomarkers rose from 6% to 29% in the placebo group, but from 3% to just 10% in those treated with canagliflozin.
“It was reassuring to discover that canagliflozin helped reduce risks the most in people with the highest chances for complications,” said Dr. Januzzi.
The CREDENCE trial and the current analysis were funded by Janssen Research & Development LLC. NT-proBNP, hs-cTnT, GDF-15, and IGFBP7 reagents were provided by Roche Diagnostics. Dr. Januzzi is funded in part by the Hutter Family Professorship. Dr. Januzzi declared relationships with Imbria Pharmaceuticals, Jana Care, Abbott, Applied Therapeutics, HeartFlow, Innolife, Roche Diagnostics, Beckman, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Merck, Novartis, Pfizer, Siemens, Abbott, AbbVie, CVRx, Intercept, and Takeda.
A version of this article first appeared on Medscape.com.
, suggests an analysis of the CREDENCE trial.
The research, published online in the journal Circulation, also revealed that patients treated with the sodium-glucose cotransporter-2 inhibitor canagliflozin (Invokana, Invokamet) had lower levels of the biomarkers after 1 year compared with those given placebo.
Examination of biomarker levels in more than 2,600 patients from CREDENCE showed that high baseline concentrations of the individual biomarkers were able to predict the future risk for a composite endpoint of renal and heart outcomes.
The combination of all four biomarkers into a single panel revealed that patients with the highest levels were more than four times as likely to experience the composite endpoint than were those with the lowest levels.
As two of the biomarkers used in the study have yet to have established prognostic thresholds, the results remain exploratory.
Lead author James L. Januzzi, MD, director of the Heart Failure and Biomarker Trials at the Baim Institute for Clinical Research, Boston, said that further study will help refine the predictive value of the panel.
“Given that the American Heart Association/American College of Cardiology and the American Diabetes Association now all recommend measurement of biomarkers to enhance the ability to predict risk in persons with type 2 diabetes, these results may considerably extend the reach of biomarker-based testing, refining accuracy even further,” he said in a press release.
In an interview, Dr. Januzzi said that “three out of the four biomarkers are already clinically and commercially available,” while the fourth, for insulin-like growth factor binding protein 7 (IGFBP7), is “on the near horizon.”
He stressed that the “future for multiple biomarker testing, however, will be less about ordering each individual test, and ultimately will revolve around panels of blood work that are ordered as a single test.”
Dr. Januzzi added that “rather than using the rather primitive approach that we took” of looking at the individual biomarkers in adjusted models, the next stage “will be to utilize algorithms to combine the results into a single value.
“A clinician will not have to struggle with looking at individual results but will just receive one aggregated test result that informs them whether a patient is at low, medium or higher risk,” he explained.
However, this will require determining the relative importance of each biomarker and weighting them in the final model.
Consequently, the current results “set the foundation for identifying some very powerful individual tests that may ultimately, in aggregate, help us to help our patients with diabetes avoid a major complication,” Dr. Januzzi said.
By revealing that some individuals with both type 2 diabetes and kidney disease are at higher risk than others, he also hopes the findings can be leveraged to treat patients with “varying degrees of intensity with proven therapies, including weight loss, dietary adjustment, and pharmacologic intervention.”
Dr. Januzzi added: “Diabetes affects a dramatic, and growing, percentage of our population, and this type of personalized strategy to reduce the major complications of this rather common disease is an important step forward.”
The authors noted that there is a “bidirectional relationship” between cardiovascular disease and chronic kidney disease (CKD), such that either diagnosis may increase the risk of, or exacerbate, the other.
Individuals with type 2 diabetes and CKD albuminuria, they added, are at particularly high risk for major cardiovascular events, and studies have shown that several circulating cardiorenal stress biomarkers may predict the onset and progression of CKD in type 2 diabetes, as well as predict cardiovascular events.
Several biomarkers associated with myocardial stress and necrosis
The recent CANVAS trial revealed that, among individuals with type 2 diabetes with and without CKD, several biomarkers were associated with myocardial stress and necrosis, and renal tubular injury, predicting the progression of CKD with albuminuria, and the risk for heart failure events.
Taking inspiration from those findings, the current researchers studied a panel of similar cardiac and renal biomarkers among participants from the CREDENCE trial, for which 4,401 patients with type 2 diabetes and CKD at high risk of progression were randomly assigned to canagliflozin or placebo.
The current analysis involved 2,627 participants who had baseline plasma samples available for analysis of four circulating biomarkers: N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), growth differentiation factor-15 (GDF-15), and IGFBP7.
Among those, 2,385 participants also had year 1 plasma samples available for analysis, while year 3 plasma samples were available for 895 individuals.
The results showed that, in general, median baseline concentrations of each biomarker in both treatment groups were elevated compared with healthy reference populations.
Baseline log-transformed concentrations of each biomarker were also strongly predictive of cardiac and renal outcomes, including heart failure and progression of CKD.
For example, each unit increase in baseline NT-proBNP concentrations was associated with a hazard ratio of 1.35 for the primary composite endpoint of end-stage kidney disease, doubling of serum creatinine levels, renal death, or cardiovascular disease (P < .001).
For each unit increase in hs-cTnT levels, the hazard ratio for the primary composite was 1.73 (P < .001), for GDF-15 it was 1.84 (P < .0001), and for IGFBP7 the hazard ratio was 3.14 (P < .001).
Combining the four biomarkers into a single multimarker panel revealed that, compared with individuals with a low-risk score, those with a high-risk score had a hazard ratio for the primary outcome of 4.01, whereas those with a moderate risk score had a hazard ratio of 2.39 (P < .001 for both).
For the individual outcome of heart failure hospitalization, the effect was even greater. A high-risk score was associated with a hazard ratio vs. a low-risk score of 6.04 (P < .001), whereas patients with a moderate risk score had a hazard ratio of 2.45 (P = .04).
The researchers also reported that, between baseline and year 1, concentrations of all four biomarkers rose from 6% to 29% in the placebo group, but from 3% to just 10% in those treated with canagliflozin.
“It was reassuring to discover that canagliflozin helped reduce risks the most in people with the highest chances for complications,” said Dr. Januzzi.
The CREDENCE trial and the current analysis were funded by Janssen Research & Development LLC. NT-proBNP, hs-cTnT, GDF-15, and IGFBP7 reagents were provided by Roche Diagnostics. Dr. Januzzi is funded in part by the Hutter Family Professorship. Dr. Januzzi declared relationships with Imbria Pharmaceuticals, Jana Care, Abbott, Applied Therapeutics, HeartFlow, Innolife, Roche Diagnostics, Beckman, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Merck, Novartis, Pfizer, Siemens, Abbott, AbbVie, CVRx, Intercept, and Takeda.
A version of this article first appeared on Medscape.com.
, suggests an analysis of the CREDENCE trial.
The research, published online in the journal Circulation, also revealed that patients treated with the sodium-glucose cotransporter-2 inhibitor canagliflozin (Invokana, Invokamet) had lower levels of the biomarkers after 1 year compared with those given placebo.
Examination of biomarker levels in more than 2,600 patients from CREDENCE showed that high baseline concentrations of the individual biomarkers were able to predict the future risk for a composite endpoint of renal and heart outcomes.
The combination of all four biomarkers into a single panel revealed that patients with the highest levels were more than four times as likely to experience the composite endpoint than were those with the lowest levels.
As two of the biomarkers used in the study have yet to have established prognostic thresholds, the results remain exploratory.
Lead author James L. Januzzi, MD, director of the Heart Failure and Biomarker Trials at the Baim Institute for Clinical Research, Boston, said that further study will help refine the predictive value of the panel.
“Given that the American Heart Association/American College of Cardiology and the American Diabetes Association now all recommend measurement of biomarkers to enhance the ability to predict risk in persons with type 2 diabetes, these results may considerably extend the reach of biomarker-based testing, refining accuracy even further,” he said in a press release.
In an interview, Dr. Januzzi said that “three out of the four biomarkers are already clinically and commercially available,” while the fourth, for insulin-like growth factor binding protein 7 (IGFBP7), is “on the near horizon.”
He stressed that the “future for multiple biomarker testing, however, will be less about ordering each individual test, and ultimately will revolve around panels of blood work that are ordered as a single test.”
Dr. Januzzi added that “rather than using the rather primitive approach that we took” of looking at the individual biomarkers in adjusted models, the next stage “will be to utilize algorithms to combine the results into a single value.
“A clinician will not have to struggle with looking at individual results but will just receive one aggregated test result that informs them whether a patient is at low, medium or higher risk,” he explained.
However, this will require determining the relative importance of each biomarker and weighting them in the final model.
Consequently, the current results “set the foundation for identifying some very powerful individual tests that may ultimately, in aggregate, help us to help our patients with diabetes avoid a major complication,” Dr. Januzzi said.
By revealing that some individuals with both type 2 diabetes and kidney disease are at higher risk than others, he also hopes the findings can be leveraged to treat patients with “varying degrees of intensity with proven therapies, including weight loss, dietary adjustment, and pharmacologic intervention.”
Dr. Januzzi added: “Diabetes affects a dramatic, and growing, percentage of our population, and this type of personalized strategy to reduce the major complications of this rather common disease is an important step forward.”
The authors noted that there is a “bidirectional relationship” between cardiovascular disease and chronic kidney disease (CKD), such that either diagnosis may increase the risk of, or exacerbate, the other.
Individuals with type 2 diabetes and CKD albuminuria, they added, are at particularly high risk for major cardiovascular events, and studies have shown that several circulating cardiorenal stress biomarkers may predict the onset and progression of CKD in type 2 diabetes, as well as predict cardiovascular events.
Several biomarkers associated with myocardial stress and necrosis
The recent CANVAS trial revealed that, among individuals with type 2 diabetes with and without CKD, several biomarkers were associated with myocardial stress and necrosis, and renal tubular injury, predicting the progression of CKD with albuminuria, and the risk for heart failure events.
Taking inspiration from those findings, the current researchers studied a panel of similar cardiac and renal biomarkers among participants from the CREDENCE trial, for which 4,401 patients with type 2 diabetes and CKD at high risk of progression were randomly assigned to canagliflozin or placebo.
The current analysis involved 2,627 participants who had baseline plasma samples available for analysis of four circulating biomarkers: N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), growth differentiation factor-15 (GDF-15), and IGFBP7.
Among those, 2,385 participants also had year 1 plasma samples available for analysis, while year 3 plasma samples were available for 895 individuals.
The results showed that, in general, median baseline concentrations of each biomarker in both treatment groups were elevated compared with healthy reference populations.
Baseline log-transformed concentrations of each biomarker were also strongly predictive of cardiac and renal outcomes, including heart failure and progression of CKD.
For example, each unit increase in baseline NT-proBNP concentrations was associated with a hazard ratio of 1.35 for the primary composite endpoint of end-stage kidney disease, doubling of serum creatinine levels, renal death, or cardiovascular disease (P < .001).
For each unit increase in hs-cTnT levels, the hazard ratio for the primary composite was 1.73 (P < .001), for GDF-15 it was 1.84 (P < .0001), and for IGFBP7 the hazard ratio was 3.14 (P < .001).
Combining the four biomarkers into a single multimarker panel revealed that, compared with individuals with a low-risk score, those with a high-risk score had a hazard ratio for the primary outcome of 4.01, whereas those with a moderate risk score had a hazard ratio of 2.39 (P < .001 for both).
For the individual outcome of heart failure hospitalization, the effect was even greater. A high-risk score was associated with a hazard ratio vs. a low-risk score of 6.04 (P < .001), whereas patients with a moderate risk score had a hazard ratio of 2.45 (P = .04).
The researchers also reported that, between baseline and year 1, concentrations of all four biomarkers rose from 6% to 29% in the placebo group, but from 3% to just 10% in those treated with canagliflozin.
“It was reassuring to discover that canagliflozin helped reduce risks the most in people with the highest chances for complications,” said Dr. Januzzi.
The CREDENCE trial and the current analysis were funded by Janssen Research & Development LLC. NT-proBNP, hs-cTnT, GDF-15, and IGFBP7 reagents were provided by Roche Diagnostics. Dr. Januzzi is funded in part by the Hutter Family Professorship. Dr. Januzzi declared relationships with Imbria Pharmaceuticals, Jana Care, Abbott, Applied Therapeutics, HeartFlow, Innolife, Roche Diagnostics, Beckman, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Merck, Novartis, Pfizer, Siemens, Abbott, AbbVie, CVRx, Intercept, and Takeda.
A version of this article first appeared on Medscape.com.
FROM CIRCULATION
Low-dose oral minoxidil for female pattern hair loss: Benefits, impact on BP, heart rate evaluated
results from a small retrospective analysis showed.
“Additionally, few patients experienced hair loss progression while slightly over a third experienced hair regrowth,” the study’s first author, Reese Imhof, MD, a third-year resident in the department of dermatology at Mayo Clinic, Rochester, Minn., said in an interview. The results were published online in JAAD International.
At low doses, oral minoxidil, approved as an antihypertensive over 40 years ago, has become an increasingly popular treatment for hair loss, particularly since an article about its use for hair loss was published in the New York Times in August 2022. (Oral minoxidil is not approved for treating alopecia, and is used off label for this purpose.)
To evaluate the effects of LDOM in female patients with female pattern hair loss, Dr. Imhof, along with colleagues Beija Villalpando, MD, of the department of medicine and Rochelle R. Torgerson, MD, PhD, of the department of dermatology at the Mayo Clinic, reviewed the records of 25 adult women who were evaluated for female pattern hair loss at the Mayo Clinic over a 5-year period that ended on Nov. 27, 2022. Previous studies have looked at the cardiovascular effects of treatment with oral minoxidil and impact on BP in men, but “few studies have reported on female patients receiving LDOM as monotherapy for female pattern hair loss,” the authors noted.
The mean age of the women in their study was 61 years, and they took LDOM for a mean of 6.2 months. Slightly more than half (52%) took a dose of 1.25 mg daily, while 40% took 2.5 mg daily and 8% took 0.625 mg daily.
Of the 25 patients, 10 (40%) had previously tried topical minoxidil but had discontinued it because of local side effects or challenges with adherence. Also, three patients (12%) had previously tried finasteride and spironolactone but discontinued those medications because of adverse side effects.
The researchers noted disease improvement and hair regrowth was observed in nine patients who were treated with LDOM (36%), while three patients (12%) had “unaltered disease progression.” Adverse side effects observed in the cohort included four patients with facial hypertrichosis (16%) and one patient with fluid retention/lower limb edema (4%).
The patients who developed hypertrichosis did not discontinue LDOM, but the patient who developed edema did stop treatment.
At baseline, systolic BP (SBP) ranged from 107-161 mm Hg, diastolic BP (DBP) ranged from 58-88 mm Hg, and heart rate ranged from 54-114 beats per minute. Post treatment, SBP ranged from 102-152 mm Hg, DBP ranged from 63-90 mm Hg, and heart rate ranged from 56 to 105 bpm. “It was surprising how little ambulatory blood pressure and heart rate changed after an average of 6 months of treatment,” Dr. Imhof said in an interview. “On average, SBP decreased by 2.8 mm HG while DBP decreased by 1.4 mm Hg. Heart rate increased an average of 4.4 beats per minute.”
He acknowledged certain limitations of the study, including its small sample size and lack of inclusion of patients who were being treated for hypertension with concomitant antihypertensive medications. “Some unique aspects of our study are that we focused on women, and we had a slightly older cohort than prior studies (61 years old on average) as well as exposure to higher doses of LDOM, with most patients on either 1.25 mg daily or 2.5 mg daily,” Dr. Imhof said.
The researchers reported having no relevant disclosures, and there was no funding source for the study.
results from a small retrospective analysis showed.
“Additionally, few patients experienced hair loss progression while slightly over a third experienced hair regrowth,” the study’s first author, Reese Imhof, MD, a third-year resident in the department of dermatology at Mayo Clinic, Rochester, Minn., said in an interview. The results were published online in JAAD International.
At low doses, oral minoxidil, approved as an antihypertensive over 40 years ago, has become an increasingly popular treatment for hair loss, particularly since an article about its use for hair loss was published in the New York Times in August 2022. (Oral minoxidil is not approved for treating alopecia, and is used off label for this purpose.)
To evaluate the effects of LDOM in female patients with female pattern hair loss, Dr. Imhof, along with colleagues Beija Villalpando, MD, of the department of medicine and Rochelle R. Torgerson, MD, PhD, of the department of dermatology at the Mayo Clinic, reviewed the records of 25 adult women who were evaluated for female pattern hair loss at the Mayo Clinic over a 5-year period that ended on Nov. 27, 2022. Previous studies have looked at the cardiovascular effects of treatment with oral minoxidil and impact on BP in men, but “few studies have reported on female patients receiving LDOM as monotherapy for female pattern hair loss,” the authors noted.
The mean age of the women in their study was 61 years, and they took LDOM for a mean of 6.2 months. Slightly more than half (52%) took a dose of 1.25 mg daily, while 40% took 2.5 mg daily and 8% took 0.625 mg daily.
Of the 25 patients, 10 (40%) had previously tried topical minoxidil but had discontinued it because of local side effects or challenges with adherence. Also, three patients (12%) had previously tried finasteride and spironolactone but discontinued those medications because of adverse side effects.
The researchers noted disease improvement and hair regrowth was observed in nine patients who were treated with LDOM (36%), while three patients (12%) had “unaltered disease progression.” Adverse side effects observed in the cohort included four patients with facial hypertrichosis (16%) and one patient with fluid retention/lower limb edema (4%).
The patients who developed hypertrichosis did not discontinue LDOM, but the patient who developed edema did stop treatment.
At baseline, systolic BP (SBP) ranged from 107-161 mm Hg, diastolic BP (DBP) ranged from 58-88 mm Hg, and heart rate ranged from 54-114 beats per minute. Post treatment, SBP ranged from 102-152 mm Hg, DBP ranged from 63-90 mm Hg, and heart rate ranged from 56 to 105 bpm. “It was surprising how little ambulatory blood pressure and heart rate changed after an average of 6 months of treatment,” Dr. Imhof said in an interview. “On average, SBP decreased by 2.8 mm HG while DBP decreased by 1.4 mm Hg. Heart rate increased an average of 4.4 beats per minute.”
He acknowledged certain limitations of the study, including its small sample size and lack of inclusion of patients who were being treated for hypertension with concomitant antihypertensive medications. “Some unique aspects of our study are that we focused on women, and we had a slightly older cohort than prior studies (61 years old on average) as well as exposure to higher doses of LDOM, with most patients on either 1.25 mg daily or 2.5 mg daily,” Dr. Imhof said.
The researchers reported having no relevant disclosures, and there was no funding source for the study.
results from a small retrospective analysis showed.
“Additionally, few patients experienced hair loss progression while slightly over a third experienced hair regrowth,” the study’s first author, Reese Imhof, MD, a third-year resident in the department of dermatology at Mayo Clinic, Rochester, Minn., said in an interview. The results were published online in JAAD International.
At low doses, oral minoxidil, approved as an antihypertensive over 40 years ago, has become an increasingly popular treatment for hair loss, particularly since an article about its use for hair loss was published in the New York Times in August 2022. (Oral minoxidil is not approved for treating alopecia, and is used off label for this purpose.)
To evaluate the effects of LDOM in female patients with female pattern hair loss, Dr. Imhof, along with colleagues Beija Villalpando, MD, of the department of medicine and Rochelle R. Torgerson, MD, PhD, of the department of dermatology at the Mayo Clinic, reviewed the records of 25 adult women who were evaluated for female pattern hair loss at the Mayo Clinic over a 5-year period that ended on Nov. 27, 2022. Previous studies have looked at the cardiovascular effects of treatment with oral minoxidil and impact on BP in men, but “few studies have reported on female patients receiving LDOM as monotherapy for female pattern hair loss,” the authors noted.
The mean age of the women in their study was 61 years, and they took LDOM for a mean of 6.2 months. Slightly more than half (52%) took a dose of 1.25 mg daily, while 40% took 2.5 mg daily and 8% took 0.625 mg daily.
Of the 25 patients, 10 (40%) had previously tried topical minoxidil but had discontinued it because of local side effects or challenges with adherence. Also, three patients (12%) had previously tried finasteride and spironolactone but discontinued those medications because of adverse side effects.
The researchers noted disease improvement and hair regrowth was observed in nine patients who were treated with LDOM (36%), while three patients (12%) had “unaltered disease progression.” Adverse side effects observed in the cohort included four patients with facial hypertrichosis (16%) and one patient with fluid retention/lower limb edema (4%).
The patients who developed hypertrichosis did not discontinue LDOM, but the patient who developed edema did stop treatment.
At baseline, systolic BP (SBP) ranged from 107-161 mm Hg, diastolic BP (DBP) ranged from 58-88 mm Hg, and heart rate ranged from 54-114 beats per minute. Post treatment, SBP ranged from 102-152 mm Hg, DBP ranged from 63-90 mm Hg, and heart rate ranged from 56 to 105 bpm. “It was surprising how little ambulatory blood pressure and heart rate changed after an average of 6 months of treatment,” Dr. Imhof said in an interview. “On average, SBP decreased by 2.8 mm HG while DBP decreased by 1.4 mm Hg. Heart rate increased an average of 4.4 beats per minute.”
He acknowledged certain limitations of the study, including its small sample size and lack of inclusion of patients who were being treated for hypertension with concomitant antihypertensive medications. “Some unique aspects of our study are that we focused on women, and we had a slightly older cohort than prior studies (61 years old on average) as well as exposure to higher doses of LDOM, with most patients on either 1.25 mg daily or 2.5 mg daily,” Dr. Imhof said.
The researchers reported having no relevant disclosures, and there was no funding source for the study.
FROM JAAD INTERNATIONAL
COVID may increase risk of high blood pressure
High blood pressure already impacts about half of U.S. adults, and the study researchers expressed concern about the sheer number of people who have newly developed the condition.
Among people in the study who had COVID but didn’t have a history of high blood pressure:
- One in five who had been hospitalized with COVID developed high blood pressure within 6 months.
- One in 10 who had COVID but were not hospitalized developed high blood pressure within 6 months.
The study appeared in Hypertension, a journal published by the American Heart Association. The researchers analyzed data for more than 45,000 people who had COVID from March 2020 to August 2022. The people did not have a history of high blood pressure. All of them were treated at the Montefiore Health System in New York, and had returned to the hospital system for any medical reason within an average of 6 months.
In an analysis to evaluate the impact of COVID, the researchers compared the likelihood of new high blood pressure in people who had the flu to the people who had COVID. The hospitalized COVID patients were more than twice as likely to get high blood pressure, compared with hospitalized flu patients. People who had COVID but weren’t hospitalized were 1.5 times more likely to get high blood pressure, compared with nonhospitalized flu patients.
People at greatest risk were age 40 or older or men, or had conditions such as chronic obstructive pulmonary disease (COPD), coronary artery disease, and chronic kidney disease.
The authors noted that the people in the study mostly lived in a low socioeconomic area, which can be a risk factor for high blood pressure. Aspects of the pandemic other than the virus itself could have impacted high blood pressure risk, too, like isolation, low activity levels, poor diet, and psychological stress. The researchers said further study is needed to overcome limitations of their research, in particular that it only included people who interacted with the health care system, and that they didn’t know if some people already had high blood pressure that was just undiagnosed.
“Given the sheer number of people affected by COVID-19, compared to influenza, these statistics are alarming and suggest that many more patients will likely develop high blood pressure in the future, which may present a major public health burden,” researcher Tim Q. Duong, PhD, professor of radiology at Albert Einstein College of Medicine and Montefiore Health System, New York, said in a statement. “These findings should heighten awareness to screen at-risk patients for hypertension after COVID-19 illness to enable earlier identification and treatment for hypertension-related complications, such as cardiovascular and kidney disease.”
A version of this article appeared on WebMD.com.
High blood pressure already impacts about half of U.S. adults, and the study researchers expressed concern about the sheer number of people who have newly developed the condition.
Among people in the study who had COVID but didn’t have a history of high blood pressure:
- One in five who had been hospitalized with COVID developed high blood pressure within 6 months.
- One in 10 who had COVID but were not hospitalized developed high blood pressure within 6 months.
The study appeared in Hypertension, a journal published by the American Heart Association. The researchers analyzed data for more than 45,000 people who had COVID from March 2020 to August 2022. The people did not have a history of high blood pressure. All of them were treated at the Montefiore Health System in New York, and had returned to the hospital system for any medical reason within an average of 6 months.
In an analysis to evaluate the impact of COVID, the researchers compared the likelihood of new high blood pressure in people who had the flu to the people who had COVID. The hospitalized COVID patients were more than twice as likely to get high blood pressure, compared with hospitalized flu patients. People who had COVID but weren’t hospitalized were 1.5 times more likely to get high blood pressure, compared with nonhospitalized flu patients.
People at greatest risk were age 40 or older or men, or had conditions such as chronic obstructive pulmonary disease (COPD), coronary artery disease, and chronic kidney disease.
The authors noted that the people in the study mostly lived in a low socioeconomic area, which can be a risk factor for high blood pressure. Aspects of the pandemic other than the virus itself could have impacted high blood pressure risk, too, like isolation, low activity levels, poor diet, and psychological stress. The researchers said further study is needed to overcome limitations of their research, in particular that it only included people who interacted with the health care system, and that they didn’t know if some people already had high blood pressure that was just undiagnosed.
“Given the sheer number of people affected by COVID-19, compared to influenza, these statistics are alarming and suggest that many more patients will likely develop high blood pressure in the future, which may present a major public health burden,” researcher Tim Q. Duong, PhD, professor of radiology at Albert Einstein College of Medicine and Montefiore Health System, New York, said in a statement. “These findings should heighten awareness to screen at-risk patients for hypertension after COVID-19 illness to enable earlier identification and treatment for hypertension-related complications, such as cardiovascular and kidney disease.”
A version of this article appeared on WebMD.com.
High blood pressure already impacts about half of U.S. adults, and the study researchers expressed concern about the sheer number of people who have newly developed the condition.
Among people in the study who had COVID but didn’t have a history of high blood pressure:
- One in five who had been hospitalized with COVID developed high blood pressure within 6 months.
- One in 10 who had COVID but were not hospitalized developed high blood pressure within 6 months.
The study appeared in Hypertension, a journal published by the American Heart Association. The researchers analyzed data for more than 45,000 people who had COVID from March 2020 to August 2022. The people did not have a history of high blood pressure. All of them were treated at the Montefiore Health System in New York, and had returned to the hospital system for any medical reason within an average of 6 months.
In an analysis to evaluate the impact of COVID, the researchers compared the likelihood of new high blood pressure in people who had the flu to the people who had COVID. The hospitalized COVID patients were more than twice as likely to get high blood pressure, compared with hospitalized flu patients. People who had COVID but weren’t hospitalized were 1.5 times more likely to get high blood pressure, compared with nonhospitalized flu patients.
People at greatest risk were age 40 or older or men, or had conditions such as chronic obstructive pulmonary disease (COPD), coronary artery disease, and chronic kidney disease.
The authors noted that the people in the study mostly lived in a low socioeconomic area, which can be a risk factor for high blood pressure. Aspects of the pandemic other than the virus itself could have impacted high blood pressure risk, too, like isolation, low activity levels, poor diet, and psychological stress. The researchers said further study is needed to overcome limitations of their research, in particular that it only included people who interacted with the health care system, and that they didn’t know if some people already had high blood pressure that was just undiagnosed.
“Given the sheer number of people affected by COVID-19, compared to influenza, these statistics are alarming and suggest that many more patients will likely develop high blood pressure in the future, which may present a major public health burden,” researcher Tim Q. Duong, PhD, professor of radiology at Albert Einstein College of Medicine and Montefiore Health System, New York, said in a statement. “These findings should heighten awareness to screen at-risk patients for hypertension after COVID-19 illness to enable earlier identification and treatment for hypertension-related complications, such as cardiovascular and kidney disease.”
A version of this article appeared on WebMD.com.
FROM HYPERTENSION